CN109481446B - Composition for improving body functions of pregnant woman, lying-in woman and lactating mother and fetus and preparation process - Google Patents

Abstract

The invention relates to a composition for improving the body functions of a pregnant woman, a lying-in woman, a lactating mother and a fetus and a preparation process thereof. In particular, one aspect of the present invention relates to a pharmaceutical composition comprising hemin and a diluent selected from the group consisting of: starch, sucrose, lactose, microcrystalline cellulose, calcium hydrogen phosphate. The invention also relates to a preparation process of the composition for improving the body functions of the pregnant woman, the lying-in woman and the fetus, and also relates to application of the pharmaceutical composition in preparing a medicine for improving the body functions of the pregnant woman, the lying-in woman, the fetus and the fetus. As stated herein, the compositions of the present invention exhibit excellent biological effects.

Description

Composition for improving body functions of pregnant woman, lying-in woman and lactating mother and fetus and preparation process

Technical Field

The invention relates to a composition for improving the body functions of a pregnant woman, a lying-in woman and a fetus and a preparation process thereof, in particular to a composition for improving the body functions of the pregnant woman, the lying-in woman and the fetus, which is prepared by taking hemin as an active ingredient, and more particularly, the composition for improving the body functions of the pregnant woman, the lying-in woman and the fetus has excellent biological effects.

Background

When the body's demand and supply of iron are unbalanced, this leads to depletion of stored Iron (ID) in the body, followed by Iron Deficiency (IDE) in the red blood cells, which ultimately leads to Iron Deficiency Anemia (IDA). IDA is the final stage of iron deficiency (including ID, IDE and IDA) and manifests as iron deficiency-induced microcytic hypopigmented anemia and other abnormalities. IDA is the most common anemia. The incidence of the disease is obviously increased in developing countries, economically undeveloped areas, infants and women of childbearing age. Survey of people in Shanghai areas shows that: the annual incidence of iron deficiency is 75.0-82.5% of infants between 6 months and 2 years old, 66.7% of women above 3 months of gestation, 43.3% of women of childbearing age and 13.2% of teenagers between 10 years and 17 years old; the prevalence rates of IDA of the above people are 33.8-45.7%, 19.3%, 11.4% and 9.8%, respectively. Iron deficiency is mainly related to the following factors: inadequate supplementary food for infants, monophagia for teenagers, menorrhagia/multiple pregnancies/lactation for women, and certain pathological factors (such as gastrostaxis, chronic blood loss, chronic diarrhea, atrophic gastritis and hookworm infection). The multiple groups of iron deficiency anemia are infants and women of childbearing age. The common symptoms of iron deficiency anemia are weakness, easy fatigue, dizziness, headache, dim eyesight, tinnitus, palpitation and the like.

Common causes of iron deficiency anemia are chronic wasting diseases, malnutrition, hookworm infection and the like. In addition, the following causes are also common causes of iron deficiency anemia: 1. iron demand increases and iron intake is insufficient: it is common in infants, teenagers, pregnant and lactating women. Infants need more iron, and are easy to lack iron if eggs, meat and other supplementary foods with higher iron content are not supplemented. Teenagers are prone to iron deficiency when eating a partiality. Women with menorrhagia, pregnancy or lactation need increased iron amount, and IDA is easily caused if high-iron food is not supplemented. 2. Iron absorption disorder: after a gastrotomy, gastric acid is not secreted sufficiently and food rapidly enters the jejunum, bypassing the main absorption site of iron (duodenum), resulting in reduced iron absorption. In addition, IDA can occur due to iron malabsorption in gastrointestinal disorders caused by various causes, such as chronic diarrhea, chronic enteritis, crohn's disease, etc. 3. Excessive iron loss: IDA results from chronic long-term iron loss that is not corrected. Such as: chronic gastrointestinal bleeding (including hemorrhoids, gastroduodenal ulcer, hiatal hernia, polyps of digestive tract, gastrointestinal tumors, parasitic infection, esophageal/gastric fundal varices, and the like), menorrhagia (gynecological diseases such as intrauterine contraceptive ring placement, hysteromyoma, menstrual disorder, and the like), hemoptysis and alveolar hemorrhage (including hemosiderosis in lung, pulmonary hemorrhage-nephritis syndrome, tuberculosis, bronchiectasis, lung cancer, and the like), hemoglobinuria (paroxysmal nocturnal hemoglobinuria, cold antibody type autoimmune hemolysis, cardiac artificial valves, marching hemoglobinuria, and the like), and others (hereditary hemorrhagic telangiectasia, chronic renal failure hemodialysis, multiple blood donations, and the like).

The treatment of anemia by the administration of ferric chloride hemoglobin is currently a clinically highly effective method. Hemin, also known as hemin, hemin hydrochloride, hemin, heme iron, etc., is an in vitro purification form of natural heme, which is generally separated and purified from animal blood. The heme iron is a pure natural biological iron supplement and has the advantages of high bioavailability, no adverse reactions such as iron accumulation poisoning in vivo, gastrointestinal irritation and the like. Experiments have proved that the absorption rate of heme iron in small intestine is only 25% at most (but not heme iron is lower, about 3% -8%), has no side reaction, is not influenced by diet and other factors, and is an ideal iron supplement. The product is more and more popular because the product can be developed into health food and beverage. Meanwhile, heme is an important raw material of anti-anemia and anti-tumor drugs, and heme of Yapeh corporation has been officially approved by FDA in USA in 7 months in 1983 to be used as a drug.

Hemin, CAS accession number 16009-13-5, molecular formula C34H32ClFeN4O4, molecular weight 651.94, chemical structural formula:

the prior art has reported a plurality of clinical treatment techniques related to hemin. For example, CN1105206A (application No. 94100393.0) relates to an iron-supplementing food additive and its preparation method, characterized in that the main component of the additive is composed of hemin extracted from animal blood and directly absorbed by intestinal wall cells, and its preparation method comprises preparing raw materials, mashing coagulated blood clot into erythrocyte liquid, adding water to make complete hemolytic liquid, adding into heated glacial acetic acid containing sodium chloride and continuously stirring, separating precipitate, washing with water, washing with ethanol, and drying to obtain the final product. The invention has no fishy smell or metallic taste, has no toxicity, accords with the hygienic standard of food additives, can be used in beverages, biscuits and candies, has no interference of other components in foods in absorption, and is superior to the common ferrous gluconate for supplementing iron and treating anemia. CN108065207A (application number: 201610996261.2) relates to a hemin health food, which comprises the following components in parts by weight: 4-8 parts of turmeric extract, 2-5 parts of Chinese date extract, 1-3 parts of dragon's blood extract, 3-6 parts of carrot extract, 2-6 parts of cowherb extract, 1-3 parts of black bean powder and 10-18 parts of hemin. The raw materials selected by the invention have scientific and reasonable mixture ratio, and human body feeding tests prove that the health-care food is suitable for anemia with reduced physiological function and malnutrition and has good improvement effect on iron-deficiency anemia, hemolytic anemia, leukemia anemia and hematopoietic disorder anemia. CN106858017A (application No. 201710045539.2) discloses an iron-rich nutritious soft candy, which contains 1-5 g/100g of hemin and 1-10 g/100g of longan extract. The invention also discloses a preparation method of the iron-rich nutritional soft sweet. The iron-rich nutritional soft sweets have excellent effects of supplementing iron and improving anemia, are good in taste and convenient to carry, and are suitable for daily health care eating of various crowds including children and pregnant women. CN103536670A (application number: 201310485725.X) relates to a composition from plants, and proposes a composition for improving nutritional anemia, which comprises the following components in parts by weight: 100-200 parts of Chinese date extract, 30-50 parts of hemin and 300 parts of auxiliary materials. The composition provided by the invention selects the jujube produced in the southern Xinjiang area, has rich nutrition and excellent qi and blood supplementing effect, and combines the hemin, thereby not only improving the condition of the spleen and the stomach of a user and enhancing the nutrient absorption, but also directly supplementing the hemin. And does not stimulate the intestines and stomach of the user. CN103005118A (application No. 201210581612.5) discloses an iron-supplementing soft sweet. The iron-supplementing soft sweets are prepared from maltitol, hemin, gelatin, pectin, agar, citric acid, malic acid and fruit juice. The iron-supplementing soft sweets are prepared by taking hemin as an iron-supplementing raw material, taking agar, gelatin, pectin and maltitol as base sugar components and adding citric acid, malic acid and fruit juice, and have excellent quality in taste, chewiness, elasticity and hardness on the basis of ensuring higher stability of the iron-supplementing soft sweets and preventing sugar body from yielding water. CN101822367A (application number: 200910079050.2) discloses a pharmaceutical composition with the function of improving nutritional anemia and a preparation method thereof. The medicine composition is prepared with spirulina phycocyanin 5-60 wt%, vitamin C2-40 wt%, vitamin B21-10 wt% and hemin 1-50 wt%. The pharmaceutical composition of the invention is believed to have the function of improving nutritional anemia.

Sufficient iron is supplemented into the donor, the body fluid balance is promoted, and the improvement of the body functions of the pregnant woman, the lying-in woman, the lactating mother and the fetus is facilitated. However, the effect of the existing hemin preparation is still improved, especially because the absorbed amount of hemin is still low. Therefore, it is still highly desirable for those skilled in the art to improve the properties of hemin to improve its clinical effect.

Disclosure of Invention

The present invention is directed to hemin compositions having superior properties, and another object of the present invention is to provide methods for preparing such compositions.

To this end, the present invention provides in a first aspect a pharmaceutical composition for improving the body function of a pregnant woman, a parturient, a pregnant woman, a fetal fetus, comprising hemin and a diluent.

The pharmaceutical composition according to the first aspect of the present invention, wherein said diluent is selected from the group consisting of: starch, sucrose, lactose, microcrystalline cellulose, calcium hydrogen phosphate, etc.

The pharmaceutical composition according to the first aspect of the present invention, further comprising a phospholipid. Such as egg yolk lecithin, soybean lecithin, etc.

The pharmaceutical composition according to the first aspect of the present invention comprises 100 parts by weight of hemin, 50 to 1200 parts by weight of a diluent, and 1 to 25 parts by weight of a phospholipid.

The pharmaceutical composition according to the first aspect of the present invention comprises 100 parts by weight of hemin, 50 to 750 parts by weight of a diluent, and 5 to 15 parts by weight of phospholipid.

The pharmaceutical composition according to the first aspect of the present invention comprises 100 parts by weight of hemin, 50 to 500 parts by weight of a diluent, and 5 to 10 parts by weight of phospholipid; for example, hemin 100 parts by weight, diluent 300 parts by weight, and phospholipid 7.5 parts by weight.

A pharmaceutical composition according to the first aspect of the present invention, which is prepared according to a process comprising the steps of: pre-pulverizing hemin into fine powder capable of passing through 100 mesh sieve; dissolving phospholipid in ethanol to prepare a solution with the concentration of 20-25%; spraying the phospholipid solution into the fine powder of hemin in a fluidized state in a fluidizing device (such as a fluidized bed granulator) at 30-35 ℃, and continuously fluidizing to remove ethanol; adding 20-30 parts by weight of diluent, uniformly mixing, and pressing the materials into a sheet-shaped object by using an extruder; freezing the sheet-like material at-20 to-15 ℃ for 24 to 30 hours; crushing the sheet, adding the rest of diluent, uniformly mixing, and continuously crushing into fine powder which can pass through a 60-mesh sieve to obtain a composition; optionally, the composition in the form of a fine powder is formulated. It has been surprisingly found that hemin in the resulting fine powder exhibits excellent dissolution and dissolution properties by pressing a hemin material into a sheet after uniformly adding a phospholipid and then freezing and pulverizing the sheet.

The pharmaceutical composition according to the first aspect of the present invention, wherein the formulation form is any suitable formulation form such as tablet, capsule, soft capsule, pill, powder, granule, electuary, oral suspension, dry suspension, ointment, jelly, and the like. The preferable preparation forms are tablets, capsules, soft capsules, granules and dry suspensions.

A further second aspect of the invention provides a process for the preparation of a pharmaceutical composition, for example a pharmaceutical composition according to any of the embodiments of the first aspect of the invention, comprising hemin and a diluent.

The method according to the second aspect of the present invention, wherein the diluent in the pharmaceutical composition is selected from the group consisting of: starch, sucrose, lactose, microcrystalline cellulose, calcium hydrogen phosphate, etc.

The method according to the second aspect of the present invention, wherein the pharmaceutical composition further comprises a phospholipid. Such as egg yolk lecithin, soybean lecithin, etc.

The method according to the second aspect of the present invention, wherein the pharmaceutical composition comprises 100 parts by weight of hemin, 50 to 1200 parts by weight of diluent, and 1 to 25 parts by weight of phospholipid.

The method according to the second aspect of the present invention, wherein the pharmaceutical composition comprises 100 parts by weight of hemin, 50 to 750 parts by weight of diluent, and 5 to 15 parts by weight of phospholipid.

The method according to the second aspect of the present invention, wherein the pharmaceutical composition comprises 100 parts by weight of hemin, 50-500 parts by weight of diluent, 5-10 parts by weight of phospholipid; for example, hemin 100 parts by weight, diluent 300 parts by weight, and phospholipid 7.5 parts by weight.

The method according to the second aspect of the invention, comprising the steps of: pre-pulverizing hemin into fine powder capable of passing through 100 mesh sieve; dissolving phospholipid in ethanol to prepare a solution with the concentration of 20-25%; spraying the phospholipid solution into the fine powder of hemin in a fluidized state in a fluidizing device (such as a fluidized bed granulator) at 30-35 ℃, and continuously fluidizing to remove ethanol; adding 20-30 parts by weight of diluent, uniformly mixing, and pressing the materials into a sheet-shaped object by using an extruder; freezing the sheet-like material at-20 to-15 ℃ for 24 to 30 hours; crushing the sheet, adding the rest of diluent, uniformly mixing, and continuously crushing into fine powder which can pass through a 60-mesh sieve to obtain a composition; optionally, the composition in the form of a fine powder is formulated. It has been surprisingly found that hemin in the resulting fine powder exhibits excellent dissolution and dissolution properties by pressing a hemin material into a sheet after uniformly adding a phospholipid and then freezing and pulverizing the sheet.

The method according to the second aspect of the present invention, wherein the formulation form is any suitable formulation form such as tablet, capsule, soft capsule, pill, powder, granule, electuary, oral suspension, dry suspension, ointment, jelly and the like. The preferable preparation forms are tablets, capsules, soft capsules, granules and dry suspensions.

According to the method of the second aspect of the invention, the prepared pharmaceutical composition is used for improving the body functions of the pregnant woman, the parturient and the fetus.

Further, the third aspect of the present invention provides a use of a pharmaceutical composition comprising hemin and a diluent in the manufacture of a medicament for improving the body function of a pregnant woman, a parturient, a fetus.

The use according to the third aspect of the invention, wherein said diluent is selected from the group consisting of: starch, sucrose, lactose, microcrystalline cellulose, calcium hydrogen phosphate, etc.

The use according to the third aspect of the present invention, wherein the pharmaceutical composition further comprises a phospholipid. Such as egg yolk lecithin, soybean lecithin, etc.

The use of the third aspect of the invention, wherein the pharmaceutical composition comprises 100 parts by weight of hemin, 50-1200 parts by weight of diluent and 1-25 parts by weight of phospholipid.

The use of the third aspect of the invention, wherein the pharmaceutical composition comprises 100 parts by weight of hemin, 50-750 parts by weight of diluent and 5-15 parts by weight of phospholipid.

The use of the third aspect of the invention, wherein the pharmaceutical composition comprises 100 parts by weight of hemin, 50-500 parts by weight of diluent and 5-10 parts by weight of phospholipid; for example, hemin 100 parts by weight, diluent 300 parts by weight, and phospholipid 7.5 parts by weight.

The use according to the third aspect of the present invention, wherein the pharmaceutical composition is prepared according to a process comprising the steps of: pre-pulverizing hemin into fine powder capable of passing through 100 mesh sieve; dissolving phospholipid in ethanol to prepare a solution with the concentration of 20-25%; spraying the phospholipid solution into the fine powder of hemin in a fluidized state in a fluidizing device (such as a fluidized bed granulator) at 30-35 ℃, and continuously fluidizing to remove ethanol; adding 20-30 parts by weight of diluent, uniformly mixing, and pressing the materials into a sheet-shaped object by using an extruder; freezing the sheet-like material at-20 to-15 ℃ for 24 to 30 hours; crushing the sheet, adding the rest of diluent, uniformly mixing, and continuously crushing into fine powder which can pass through a 60-mesh sieve to obtain a composition; optionally, the composition in the form of a fine powder is formulated. It has been surprisingly found that hemin in the resulting fine powder exhibits excellent dissolution and dissolution properties by pressing a hemin material into a sheet after uniformly adding a phospholipid and then freezing and pulverizing the sheet.

The use according to the third aspect of the present invention, wherein the formulation is in the form of a tablet, capsule, soft capsule, pill, powder, granule, electuary, oral suspension, dry suspension, ointment, jelly, or any other suitable formulation. The preferable preparation forms are tablets, capsules, soft capsules, granules and dry suspensions.

In describing the method steps of the present invention, although the particular steps described are distinguished in some detail or language from the steps described in the examples of the detailed description which follow, those skilled in the art can nevertheless fully appreciate the above-described method steps from the detailed disclosure throughout the present application.

Any embodiment of any aspect of the invention may be combined with other embodiments, as long as they do not contradict. Furthermore, in any embodiment of any aspect of the invention, any feature may be applicable to that feature in other embodiments, so long as they do not contradict.

The invention is further described below.

All documents cited herein are incorporated by reference in their entirety and to the extent such documents do not conform to the meaning of the present invention, the present invention shall control. Further, the various terms and phrases used herein have the ordinary meaning as is known to those skilled in the art, and even though such terms and phrases are intended to be described or explained in greater detail herein, reference is made to the term and phrase as being inconsistent with the known meaning and meaning as is accorded to such meaning throughout this disclosure.

The most common cause of anemia is iron deficiency anemia or nutritional anemia. If the iron intake of a human body is insufficient, hemoglobin synthesis is affected, so that the content of hemoglobin in red blood cells is remarkably reduced, and the number of red blood cells is reduced. As a result, oxygen supply to cells and tissues in the human body becomes insufficient, resulting in iron-deficiency anemia.

Anemia patients are most frequently preschool children, pregnant women and women of childbearing age, and are one of important nutritional deficiency diseases in the world. According to the research of the institute of nutrition and food hygiene, national academy of preventive medicine sciences, in 1986, of 4747 preschool children, patients with iron deficiency anemia accounted for 59.1%, and the prevalence was highest in children from 6 months to 1 year. The examination of several nurses in Shanghai in 1990 shows that the iron-deficiency anemia of infants is common, and accounts for about 30-40% of the number of examined people. In autumn, Zhejiang province in 1984, 33.1% of 1035 people were iron-deficient in hemoglobin. Wherein the urban residents account for 51.9 percent, the farmers account for 40.1 percent, the college students account for 48.3 percent, and the urban primary school students account for 68.3 percent. According to the investigation of iron intake, the iron intake of various people in Zhejiang province is 18.0-88.3 mg, which accounts for 180-736% of the standard supply amount. This indicates that the iron source is quite abundant in view of the iron content of the food. Again from a food category, the iron source is mainly from vegetable food. However, plant foods have very low iron absorption. For example, only 1% for rice, 5% for wheat, 7% for spinach and soybeans. In contrast, meat and liver absorption is high, about 22%. If the average absorption rate of the iron in the food is 10%, the average amount of the iron absorbed and utilized per person per day is only 1.8-8.88 mg. Of course, this situation has improved in recent years, but the iron utilized is still insufficient. Thus, in addition to paying attention to the supplementation of iron in the diet, another important factor is that further efforts must be made to improve the absorption and release and availability of iron.

In the aspect of main symptoms of iron deficiency anemia, hemoglobin is a red iron-containing protein, wherein the amount of iron accounts for about 70-80% of the total iron content of a human body. The main component of red blood cells is hemoglobin. The work of oxygen transport by erythrocytes is done by means of hemoglobin. Iron is a valence-variable element and comprises three types, namely ferroferric oxide, ferric oxide and ferrous oxide. Iron is a good carrier of oxygen in blood because it requires very little energy to be consumed (or evolved) when changing from one valence state to another. When blood enters the lung, iron in the red blood cells is combined with fresh oxygen, and the iron is changed from low price to high price; when blood enters other parts of the body, iron in the red blood cells changes from high valence to low valence and releases oxygen. At this time, the main symptoms are represented as: first, due to insufficient oxygen supply, blood in the body flows more to important organs, and blood vessels of organs that are not temporarily affected, for example, skin and mucous membrane, start to contract. Whitening of the skin, mucous membranes within the eyelids, etc. often occurs. This phenomenon is particularly evident in the lips, nails and earlobes. ② the body will have various discomfort due to the insufficient oxygen supply to the cells: shortness of breath, accelerated heartbeat, fatigue, susceptibility to fatigue, loss of appetite, lethargy and the like. And iron-deficiency anemia can easily cause hypoxia in brain, influence normal thinking, cause poor thinking ability and amnesia, and cause dizziness, dim eyesight, tinnitus and the like frequently. For infants under 2 years old, the normal development of brain and body is directly influenced. In addition, iron deficiency can affect protein synthesis and energy utilization, damage immune mechanisms of human bodies, cause disorder of inorganic salt and vitamin metabolism, lead retention, increase absorption of magnesium, cobalt and zinc, reduce content of vitamin C in blood and increase number of platelets. It also causes the transformation ratio of drug action and metabolism in vivo, and increases the excretion amount of succinic acid and ketone body in urine.

Iron deficiency anemia develops slowly. When the daily intake of iron is insufficient, anemia does not occur immediately, but rather iron stored in the body is utilized. When the iron in the stock is used up and the tendency to develop anemia begins, the symptoms do not immediately appear, and even most people feel unnoticeable even by themselves. When a patient visits a hospital, the condition typically develops moderate anemia. Therefore, the health of the body can be ensured by paying attention to iron supplementation and storing a certain amount of iron in the body.

Hemin is a heme crystal purified from animal blood and has chemical properties similar to those of heme. Hemin is crystal or powder, the light transmission is black brown, the refraction is steel blue, no odor and tasteless, is insoluble in water and acetic acid, is slightly soluble in 70% -80% ethanol, is dissolved in acidic acetone, is dissolved in dilute sodium hydroxide solution, and generates hemin in sodium hydroxide solution.

Heme is mainly present in the blood and muscle of animals and is a natural pigment in the blood of animals. The heme is formed by complexing protoporphyrin IX and Iron (II), has blue-black crystal, is insoluble in water, is soluble in acidic acetone and alkaline aqueous solution, and is easy to form a polymer in the solution. The molecule has resonance structure and stable property. Can be combined with protein to form complex protein, i.e. hemoglobin (Hb) or myoglobin (Mb). Hb is transport O₂And a portion of CO, which is a buffer substance to maintain the pH of the blood constant. Under certain conditions, the heme can be separated from the protein.

Hemin is generally extracted from pig blood, and has wide application in the industries of medicine, food, chemical industry, health products, construction and cosmetics. In the food industry, hemin can replace color former nitrite and artificial synthetic pigment in meat products; in the pharmaceutical industry, it can be used as a semi-synthetic bilirubin raw material and can be used for preparing anticancer specific drugs; clinically, it can be made into heme iron supplement; it is an important raw material in the cosmetic industry.

The hemin is used as iron enhancer, and has the advantages of high bioavailability, no adverse reaction such as iron accumulation poisoning in vivo and gastrointestinal irritation, etc. This is because hemin is absorbed in molecular form and can be taken up directly by the intestinal mucosa. The hemin is a biological iron source which is generally accepted by modern medicine and has high absorption rate and good effect for preventing and treating iron-deficiency anemia, has no iron fishy smell, does not stimulate the stomach and intestine, and is a preferred iron-supplementing and blood-enriching product for infants and pregnant women.

The current articles and reports about the hemin detection method mainly include an ultraviolet spectroscopy method, a fluorescence method, an infrared spectroscopy method, a polarography method, a visible light spectrophotometry method, an electrode method and the like. Ultraviolet and infrared spectroscopy: the two spectroscopy principles are similar, and the infrared scanning spectrogram and the ultraviolet scanning spectrogram of the standard substance and the sample are compared to compare the trend and the variation trend of the spectrograms. In the infrared scanning spectrum, if the sample and the standard have the same absorption characteristics, the shape of the scanning spectrum is substantially consistent, which indicates that the sample obtained by the test is hemin. In the ultraviolet scanning spectrum, the standard substance has maximum absorption in the range of 380-410nm, but the maximum absorption wavelength of the standard substance is different due to the difference of solvents. Under the same experimental conditions, if the sample has maximum absorption at the same wavelength, the method can be used as a qualitative identification of hemin. The content of hemin in the hemin oral liquid is detected by using a Yuan-xi method through ultraviolet spectroscopy, and hemin in paradeficient oral administration is detected at a wavelength of 384nm, and the result shows that in a linear range of 1.80-9.10ug/mL, R is 0.9999, the standard deviation is 0.67%, and the average recovery rate of the method reaches 99.3%. The fluorescence method is to utilize the fluorescence characteristic of porphyrin in heme and detect the fluorescence intensity of a sample by a fluorescence photometer so as to calculate the corresponding heme content, for example, the quantitative determination of heme in feces, hemoglobin is digested into heme in intestinal tracts, most of heme is digested into porphyrin under the action of bacteria in the intestinal tracts, and the corresponding heme content can be calculated by utilizing the fluorescence characteristic of porphyrin. The heme and the oxalic acid reagent can remove ferrous ions through heat energy and are reduced into porphyrin with fluorescence characteristics, and under the condition, the porphyrin measured by a fluorescence method is the total heme amount in the intestinal tract. The intestinal conversion rate of the hemoglobin is obtained by dividing the total amount of the hemoglobin by the digested hemoglobin, and the intestinal conversion rate is higher as the bleeding part is higher and the digested and absorbed time is longer, so that the intestinal bleeding part can be roughly calculated from the intestinal conversion rate. Visible light spectrophotometry: dissolving heme in 0.25% Na2CO3 solution, and determining heme content by using the method in the process of extracting heme by hydrochloric acid acetone method with yangshuqin, wherein the maximum absorption peak value exists at the wavelength of 610 nm. Polarography: by studying the polarographic behavior of hemoglobin, with 0.1mol/LNH3-NHCl as the buffer solution, hemoglobin showed a sensitive cathodic wave at-0.42V. The method can detect the minimum hemoglobin concentration of 8 × 10 mol/L. Electrode method: the method adopts the modified graphite electrode to detect the heme, finds that the electrode reacts sensitively to the concentration of the heme, and the heme and the electrode react in a linear relation within the range of 1 × 10-1 × 10 mol/L. Other methods are as follows: in addition to the above methods, there are some methods for measuring hemin. Dissolving hemin in sodium hydroxide solution under heating in water bath, cooling, adding sulfuric acid, and shaking to obtain brown precipitate. After filtering, adding a few drops of ammonium thiocyanate test solution into the filtrate, wherein the solution is brownish red. The color reaction can be used for qualitative detection of hemin.

The causes of iron deficiency anemia are mainly, 1. iron demand is increased and iron intake is insufficient: it is common in infants, teenagers, pregnant and lactating women. The iron requirement of infants is higher, and if the infants do not supplement supplementary foods with higher iron content such as eggs and meat, iron deficiency is easily caused. Teenagers are prone to iron deficiency when eating a partiality. Women with menorrhagia, pregnancy or lactation need increased iron amount, and IDA is easily caused if high-iron food is not supplemented. 2. Iron absorption disorder: after a gastrotomy, gastric acid is not secreted sufficiently and food rapidly enters the jejunum, bypassing the main absorption site of iron (duodenum), resulting in reduced iron absorption. In addition, IDA can occur due to iron malabsorption in gastrointestinal disorders caused by various causes, such as chronic diarrhea, chronic enteritis, crohn's disease, etc. 3. Excessive iron loss: IDA results from chronic long-term iron loss that is not corrected. Such as: chronic gastrointestinal bleeding (including hemorrhoids, gastroduodenal ulcer, hiatal hernia, polyps of digestive tract, gastrointestinal tumors, parasitic infection, esophageal/gastric fundal varices, and the like), menorrhagia (gynecological diseases such as intrauterine contraceptive ring placement, hysteromyoma, menstrual disorder, and the like), hemoptysis and alveolar hemorrhage (including hemosiderosis in lung, pulmonary hemorrhage-nephritis syndrome, tuberculosis, bronchiectasis, lung cancer, and the like), hemoglobinuria (paroxysmal nocturnal hemoglobinuria, cold antibody type autoimmune hemolysis, cardiac artificial valves, marching hemoglobinuria, and the like), and others (hereditary hemorrhagic telangiectasia, chronic renal failure hemodialysis, multiple blood donations, and the like).

The clinical manifestations of iron deficiency anemia mainly include the following aspects, 1. the onset manifestations of iron deficiency are: such as women with excessive menstrual flow, digestive ulcer/tumor/black stool/bloody stool/abdominal discomfort caused by hemorrhoid, abdominal pain/stool character change caused by intestinal parasite infection, marasmus of tumor diseases, hemoglobinuria, etc. 2. The anemia is manifested as: debilitation, tiredness, dizziness, headache, dim eyesight, tinnitus, cardiopalmus, short breath, anorexia, pallor, and increased heart rate. 3. The iron deficiency of the tissue is shown as follows: abnormal mental behaviors such as dysphoria, irritability, inattention, pica; physical strength and endurance decline; the infection is easy; growth and development retardation and mental retardation of children; stomatitis, glossitis, atrophy of tongue papilla, chapped corners of mouth, dysphagia; dry and dry hair and loss; dry and wrinkled skin; the nail is lack of luster, brittle, thin and easy to crack, and the nail becomes flat even concave like a spoon (reverse nail) in case of heavy nail.

Whether iron deficiency anemia occurs or not can be judged by the following examination, 1. hemogram, which shows microcytic hypopigmented anemia. Mean Corpuscular Volume (MCV) <80fl, mean corpuscular hemoglobin content (MCH) <26pg, Mean Corpuscular Hemoglobin Concentration (MCHC) less than 0.32. Small red blood cells and enlarged central superficial zone can be seen in the blood slice. More reticulocyte counts were either normal or slightly elevated. White blood cell and platelet counts can be normal or reduced. 2. Myeloid picture, hyperplastic or apparently active; mainly takes the red system hyperplasia as the main part, and the grain system and the megakaryosystem have no obvious abnormality; the erythroid is mainly composed of middle and late erythroblasts, and has small volume, compact chromatin, little cytoplasm, irregular edge, and poor hemoglobin formation (aged plasma juvenile). 3. Iron metabolism, after staining the bone marrow smear with potassium ferrocyanide (Prussian blue reaction), there are no dark blue iron-containing hemoxanthin particles in the bone marrow granule, the iron granule in the erythroid is reduced or disappeared, the number of iron granule immature cells is less than 0.15; serum ferritin reduction (<12 μ g/L); serum iron decreased (<8.95 μmol/L), total iron binding increased (>64.44 μmol/L), transferrin saturation decreased (< 15%). The concentration of sTfR (soluble transferrin receptor) exceeds 8 mg/L. 4. Porphyrin metabolism in erythrocytes, FEP (erythrocyte free protoporphyrin) > 0.9. mu. mol/L (whole blood), ZPP (zinc protoporphyrin) > 0.96. mu. mol/L (whole blood), FEP/Hb (hemoglobin) > 4.5. mu.g/gHb.

The microcytic anemia, iron granulocytic anemia, is further identified by the following differential diagnosis: red blood cell iron utilization aplastic anemia caused by heredity or unknown reasons. The small cell anemia is shown, but the serum ferritin concentration is increased, the bone marrow granule contains ferrihemoxanthin particles and sideroblasts are increased, and the annular sideroblasts are appeared. Serum iron and iron saturation are increased, and total iron binding capacity is not low. 2. Thalassemia: there is a family history. There is a manifestation of hemolysis. A large number of target red blood cells are visible in the blood sheet. Fetal hemoglobin or hemoglobin a2 is increased. Serum ferritin, bone marrow stainable iron, serum iron and iron saturation are not low and are often increased. 3. Anemia of chronic disease: anemia of iron metabolism abnormality caused by chronic inflammation, infection or tumor. Anemia is microcytic. Iron stores (serum ferritin and bone marrow granules containing haemagglutinin) increase. Serum iron, serum iron saturation, and total iron binding are reduced. 4. Transferrin deficiency: autosomal recessive inheritance (congenital) or severe liver disease, tumor secondary (acquired). Manifested as microcytic hypopigmented anemia. Serum iron, total iron binding force, serum ferritin and bone marrow containing iron hemoxanthin are all obviously reduced. Congenital diseases, infant diseases, accompanied by poor development and multi-organ function. Acquired and has the primary manifestation of disease.

The treatment of iron deficiency anemia is mainly carried out from the following aspects, 1. treatment principle: the principles for treating IDA are: firstly, the cause of the disease is radically cured; ② supplementing iron storage. 2. The etiology and treatment are as follows: the diet should be improved for IDA caused by insufficient nutrition in infants, adolescents and pregnant women. IDA caused by menorrhagia should regulate menstruation. Parasite infections should be treated for anthelmintic treatment. Malignant tumor, should be operated or radiotherapy, chemotherapy; for ulcer of upper digestive tract, acid suppression treatment should be used. 3. Iron supplement treatment: the therapeutic iron agent includes inorganic iron and organic iron. The inorganic iron is represented by ferrous sulfate, and the organic iron comprises iron dextran, ferrous gluconate, ferric sorbitol, ferrous fumarate, polysaccharide-iron complex, etc. The side reaction of the inorganic iron agent is more obvious than that of the organic iron agent. Oral iron preparation is preferred. Such as: ferrous sulfate or iron dextran. After meal, the gastrointestinal tract reaction is small and easy to tolerate. Eating cereals, milk and tea can inhibit iron absorption, and fish, meat and vitamin C can enhance iron absorption. The effective expression of the oral iron preparation is that the peripheral blood reticulocyte is increased firstly, the peak is 5-10 days after the start of taking the iron preparation, the hemoglobin concentration is increased after 2 weeks, and the iron preparation is recovered to be normal generally about 2 months. The iron treatment should be continued for 2-3 months after the hemoglobin returns to normal, and the iron treatment should be stopped after the hemoglobin is normal. If the oral administration of the iron preparation cannot tolerate or the normal anatomical parts of the gastrointestinal tract are changed to influence the absorption of iron, the iron preparation can be injected intramuscularly. Prognosis of iron deficiency anemia: the patients with simple nutrition deficiency are easy to recover to normal; secondary to other diseases, depending on whether the primary disease can be cured radically. Prevention of iron deficiency anemia: emphasis is placed on nutrition and health care of infants, teenagers and women; for infants, foods rich in iron, such as eggs, liver, spinach, etc., should be added as soon as possible; for teenagers, the preference should be corrected, and the parasitic infection should be checked and treated regularly; can be used for pregnant women and lactating women for supplementing ferrum; it is suitable for women in menstrual period for preventing and treating menorrhagia. The prevention and treatment of the crowds with the neoplastic diseases and the chronic hemorrhagic diseases are well performed.

Qi-blood deficiency refers to qi deficiency and blood deficiency in traditional Chinese medicine. The traditional Chinese medicine considers that 'qi' and 'blood' are basic substances for forming and maintaining life activities of human bodies, people are easy to sleep in spring just because of deficiency of qi and blood, and sleep can just nourish qi and blood, so people are more sleepy than other seasons. People with qi deficiency are prone to fatigue, cannot keep working and often have weakness in limbs. The traditional Chinese medicine has knowledge of deficiency of qi and blood: qi is a delicate substance that travels in the human body. Has strong energy activity to stimulate and promote the function of organs of the body, thus representing the qi of five zang organs and the qi of meridians. Qi plays a major role in warming the body and resisting the invasion of exogenous pathogens, and also participates in the metabolism of visceral functions. Blood is the red fluid flowing in the meridians. Blood functions in two ways. First, it is to nourish the zang-fu organs, body constituents, meridians and orifices. Blood exuberance can make the body healthy, the face ruddy, the skin smooth, the hair moist and the joints flexible. Secondly, blood is the material basis for mental activities. Exuberant blood can induce the mind to refresh qi and induce quick thinking. Blood deficiency is marked by absentmindedness, palpitation and uneasiness. The deficient qi and blood can cause the hypofunction of zang-fu organs, leading to premature senility. Qi deficiency means the hypofunction of the zang-fu organs and poor resistance to disease, manifested as aversion to cold, cold limbs, spontaneous perspiration, dizziness, tinnitus, listlessness, fatigue, weakness, palpitation, shortness of breath and hypoevolutism. Blood deficiency can lead to lusterless sallow complexion, dry skin, withered hair, dry nails, dim eyesight, numb hands and feet, insomnia, dreaminess, amnesia, palpitation and absentmindedness. Deficiency of both qi and blood pertains to both qi and blood disorders. Qi and blood deficiency can cause malnutrition of the body, with the common symptoms of lassitude, shortness of breath, laziness in speaking, pale or sallow complexion, dizziness, pale lips and nails, palpitation, insomnia, pale tongue and weak pulse. The common causes are: qi deficiency results in blood deficiency, and qi and blood deficiency due to long-term illness. Common symptoms are: aversion to cold, cold limbs, spontaneous perspiration, dizziness, tinnitus, fatigue, weakness, palpitation, etc. Qi and blood are the material basis for maintaining the normal functions of the body, and can promote blood circulation, and blood can transport carrier gas, so that qi and blood are bred, and qi deficiency results in blood deficiency and blood deficiency results in qi deficiency. The chronic disease impairs qi and blood, resulting in deficiency of both qi and blood. The clinical manifestations of deficiency of qi and blood are deficiency of qi and blood, weak constitution, aversion to cold, cold limbs, spontaneous sweating, dizziness, tinnitus, fatigue, weakness, palpitation, shortness of breath and hypoevolutism due to qi deficiency. Blood deficiency can lead to lusterless sallow complexion, dry skin, withered hair, dry nails, dim eyesight, numb hands and feet, insomnia, dreaminess, amnesia, palpitation and absentmindedness. Deficiency of qi and blood can lead to fatigue, shortness of breath, no desire to speak, pale or sallow complexion, dizziness, pale lips and nails, palpitation, insomnia, scanty menstruation, delayed or amenorrhea, pale tongue and weak pulse. The main syndrome of deficiency of both qi and blood: sallow complexion, shortness of breath, no speaking desire, lassitude, hypodynamia, dizziness, palpitation, poor sleep, poor appetite, pale tongue and soft and thready pulse. The deficiency of qi and blood can be judged from the following aspects: 1. eye: the color and clarity of the eyes, the white color of the eyes becomes turbid, yellow and bloody, indicating insufficiency of qi and blood. 2. Skin: the white and pink skin has luster, elasticity, no wrinkles and no spots, and represents the sufficiency of qi and blood of the lung. Rough skin, no luster, dark, yellow, white, bluish, red, and blotchy skin, indicating poor condition and deficiency of qi and blood. 3. Hair: the growth rate of hair is related to liver blood, if liver blood is insufficient, hair grows slowly, hair is dry and falls off, hair is yellow, white and split, which indicates that qi and blood are insufficient, and liver blood and kidney qi decline. 4. Gingiva: gingiva is associated with the stomach and intestine, and gingival atrophy represents a deficiency of qi and blood. 5. Nail: there is no semilune on the finger or semilune on the thumb, and longitudinal striation appears on the nail, indicating that the body is heavy in cold and qi, deficiency of both qi and blood, and overdraft appears, which is the sign of aging of the body. 6. Finger: the finger is full, and the flesh is elastic, indicating sufficient qi and blood; a flat, weak finger or thin finger tip indicates insufficient qi and blood. 7. Sleeping: the sleep is fast, the sleep is deep, the breathing is uniform, and the people can sleep to wake naturally, which indicates that the qi and blood are sufficient; difficulty in falling asleep, easy fright and easy wakening, profuse urine at night, deep and heavy breath or snore, which indicates deficiency of both qi and blood. 8. And (3) movement: the state of chest distress, short breath and fatigue difficult to recover during exercise indicates that the qi and blood are insufficient. 9. Temperature of the hand: hands are warm with sufficient qi and blood; if the palm is hot or sweaty or cold, it is the manifestation of deficiency of qi and blood. Briefly, deficiency of qi and blood means movement asthma and palpitation, while deficiency of blood means yellow complexion, whitish complexion, dizziness, palpitation and poor sleep.

Aging refers to the phenomenon that the physiological and psychological adaptive abilities of the body to the environment are progressively reduced and gradually die. Aging can be divided into two categories: physiological aging and pathological aging. The former refers to a physiological degenerative process occurring after maturation and the latter is an aging change due to various external factors including various diseases. The two are practically indistinguishable. In summary, aging is a corollary of the combined effects of many pathological, physiological and psychological processes, the biological psychological process of the final stages of growth and development of an individual. Biologically, aging is a spontaneous inevitable process of an organism over time, and is a complex natural phenomenon, which is manifested by degenerative changes in structure and functional decline, and decline in adaptability and resistance. Physiologically, aging is considered as a history of ontogeny proceeding from the fertilized egg to the elderly. Pathologically, aging is the result of stress and strain, injury and infection, decline in immune response, nutritional imbalance, metabolic disorders, and the accumulation of negligence and abused drugs. In addition, from the sociology, the aging is that the individual loses interest in fresh things, is out of reality and likes nostalgic. One of the activities accompanying the life development and development process is the loss and degeneration of the body from the constituent materials and tissue structures to physiological functions. The aging process is continued from the fertilized egg to death, and the aging characteristics are only obviously shown until a certain stage. The physiological changes in the aging process of human body are mainly reflected in the loss of organism tissue cells and constitutional substances, the slowing of organism metabolic rate and the hypofunction of organism and organs. Senescence is inevitable, but delaying senescence is possible. The reasonable diet and the balanced nutrition are one of the important measures for delaying the aging and prolonging the life. The main physiological manifestations of aging are: (1) and (4) changing the form. The method comprises the following steps: (ii) a cellular change. Mainly manifested as a gradual decrease in cell number. Variation of tissues and organs. Atrophy and weight loss occur due to the decrease in the number of cells in internal organs and tissues. And integral change. Changes in body shape and appearance, such as hair whitening, occur with age; the elasticity of the skin is reduced, wrinkles appear, and age spots appear; loose and fallen teeth, deafness, dim eyesight, hunchback, and gradually shortened height. (2) Physiological function declines. The method comprises the following steps: decline of cardiovascular system function. For example, the cardiac fibers gradually shrink, the senile pigment (lipofuscin) in the cardiac muscle cells is deposited, and the cardiac valves become thick and hard, the elasticity is reduced, and the like. ② the aging of respiratory organs. It is manifested as a decrease in lung volume, a significant decrease in respiratory function, and a decrease in compensatory ability. ③ changes in the digestive system. Mainly, the function of the oral cavity and the stomach and intestine is weakened, and the gingiva and the teeth are atrophically changed. Fourthly, the variation of the musculoskeletal movement system. Mainly characterized by the thinning of muscle fiber, the reduction of elasticity and the weakening of contractility with the age; the organic components in the bone are reduced, and the inorganic salt is increased, so that the flexibility of the elasticity of the bone is reduced, and the bone is easy to fracture. Nervous system changes. Mainly manifested as some degree of loss of brain cells; a decrease in nerve conduction velocity; the elderly have sluggish movements, reduced response dexterity, etc. (3) The main sensory organ functions decline. Such as visual, auditory, olfactory, gustatory, and cutaneous sensory (including tactile, temperature, and pain) abilities. In addition, mental motor responses of the elderly are correspondingly sluggish. Aging itself has 6 major characteristics, i.e.: i.e., all organisms will age. Second, inherent property: the aging process is a spontaneous inevitable process in the body, i.e., the aging process is gradually progressed even when living in an optimum environment. ③ progressive: aging is a process that continues to progress over time. Harmfulness: aging reduces the physiological functions of the organism, increasing the chances of illness and death. Individual difference: the aging process varies among individuals within the same organism, and this difference is more pronounced, particularly later in life. Longevity is only possible in those individuals who are slow aging. Interference: although aging is an inherent, spontaneous process, external conditions can accelerate or retard the progression of this process. Such as ambient temperature, can alter the longevity of the animal. Therefore, it is possible to improve the living environment and to prolong the life. Physiologically, aging is caused by hypometabolism. Metabolism is one of the basic features of life activities, and includes both anabolism and catabolism. If the anabolism of the organism is higher than the catabolism, the human body can grow and develop, namely childhood and juvenile; if the speeds of the two metabolic processes are basically balanced, the human body reaches the middle age and the strong age, and the change of the human body is small in the middle age and the strong age; if catabolism is higher than anabolism, a person begins to age, and if metabolism ceases, the person's vital activities end. Such changes are ubiquitous throughout a person's lifetime, and thus aging is inevitable. However, in a person's lifetime, the aging process occurs early, either for intrinsic or extrinsic reasons, which is premature aging. Premature aging is pathological aging that affects the life of a person. Pathological aging is likely to occur in the elderly, but not necessarily in every person. Physiological aging is therefore an inevitable natural law, whereas pathological aging is prevented and delayed. In order to combat aging, the mechanisms of aging have been extensively studied. However, the mechanism of aging has not been completely understood so far. Briefly, the apparent outward manifestations of aging are: poor physical strength, easy insomnia, hearing loss, heavy taste, high blood pressure, alopecia, etc.

The immunity is a protective physiological reaction of the body, the balance and stability of the internal environment are maintained through the immune function, and the immune diseases are caused by the abnormal immune function. According to the research of the American immune scientist, most of the diseases of human beings are attributed to the problems of the immune system. Long-term mental stress has an important influence on the immune function of a human body, and professor thomas of the Hopkins medical college of America observes 1337 volunteers for 18 years, and finds that if a person is in an isolated, contradictory, disappointing and depressed state for a long time, the balance of the internal environment is influenced, so that the resistance is weakened. In modern cities, the health of each person is easily threatened, including air pollution, water pollution, environmental pollution, working pressure, economic pressure, improper diet, bacteria and viruses, and all the factors which are unfavorable for health can cause low immunity of the organism, and generally show that people cannot concentrate, have poor memory, are frequently tired, are susceptible to diseases, age in advance and the like. Particularly, some people who take mental labor as occupation have large relative mental stress, so that the mental stress is accumulated for a long time, and the brain is overloaded and operated, thereby causing the immunity to be reduced, the whole body to be weak, the head to be dizzy and the eyes to be astringent, the palpitation to be short of breath, the insomnia to be forgetful, and the like. People with low immunity are susceptible to cold and epidemic diseases, people with low immunity are easy to infect the people with low immunity for a long time than healthy people, and bacteria, viruses and the like can be gathered in the body to cause diseases of the human body due to the damage of the immune system caused by any reason. The immune system in the human body is the best defense weapon, which has the function of defending against the invasion of pathogenic microorganisms and the like. Immunization serves as a biological response process that "recognizes" and "excludes" non-native antigens to maintain physiological equilibrium in the body. The immunity function is the basis of human health, and when the immunity function is disordered and low, the immunity function can reduce the infection resistance of the organism, reduce the capacity of identifying and eliminating self-aged histiocyte, and reduce the capacity of killing and eliminating abnormal mutant cells in the body, thereby reducing the disease resistance and self-healing capacity of the human body. In modern society, the pace of life is accelerated, and the competitive pressure is increased, so that many people are in a nervous working and learning state, and the organism can inhibit the immunologic function after being in the nervous state for a long time; meanwhile, more people have to eat convenient fast food due to intense work and study, unbalance of nutrients in the body is caused, and if the body is in the state for a long time, the immunity of the body is reduced, and finally the sub-health state of the body is caused.

The human microcirculation is the circulation dynamics of body fluids (blood, lymph, interstitial fluid) directly involved in the exchange of cells and tissue substances. Blood is flowing and circulating, and the most fundamental function of blood circulation is to exchange substances between blood and tissues, which is achieved in microcirculation. Therefore, microcirculation is an important component of the whole body blood circulation, is the basic link of life, and is the process of continuously exchanging substances, energy and information between the body and the surrounding environment. After being pumped out by the heart, the blood of the human body flows from the aorta to the arteriole, then enters the capillary vessel and then flows back to the heart through the venules and veins at all levels. This blood circulation between the oligodynamic and the venules is called microcirculation. In medicine, microcirculation also includes the microcirculation of lymph and interstitial fluid, but microcirculation is generally referred to as blood microcirculation. The microcirculation has four characteristics, namely longest, thinnest and slowest small blood vessels, and is knitted into a supply network which is distributed all over the body. Thinning: the diameter of the arteriole and the venule is very small, only 1/20 hairs are allowed to pass through, and only 1-2 red blood cells are allowed to pass through; thinning: the wall of the arteriole and the venovel is thin, and only one piece of paper 1/100 is provided for exchanging substances with tissue cells, and the substance exchange between the tissue cells is influenced once the wall is thickened; length: the arteriole and the venule of a normal person are added together and can wind the earth for two and a half circles; slow speed: the blood flow speed in the arteriole and the venule is very slow, the flow speed is 1 mm/s, when the blood viscosity is increased, the blood flow speed is slower, and blood contents are easily deposited on the blood vessel wall to form embolism and block the blood vessel. The major functions of the microcirculation are to achieve the exchange of substances between blood and tissue cells, transport nutrients (including nutrients and oxygen) and discharge waste products (including metabolites and carbon dioxide). The blood vessel of the microcirculation is the thinnest, the tube wall is the thinnest, the blood flow is the most suitable, the blood vessel is the real nutrition blood vessel of the tissue cell, and the blood vessel of the microcirculation can allow oxygen and carbon dioxide to pass; glucose and amino acid can pass through; saline and other nutrients may be allowed to pass through. The microvessels provide sites for exchange of material metabolism, and the material exchange process is completed by microcirculation. Therefore, the normal metabolism of tissue cells of the whole body is ensured, and the living functions of human activities are maintained. In conclusion, microcirculation is the base for the growth and development of the body, and can play a role in regulating the metabolic activity mechanism of the body at various ends through tissue perfusion, thereby ensuring the balance of the internal environment. Whether the microcirculation is normal or not is an important sign of the health status of the human body. Microcirculation is the place where the cells of human tissue absorb nutrients and oxygen and discharge metabolites. The human body cannot directly perfuse blood to tissue cells of each organ of the human body by the contraction force of the heart, and the blood must be secondarily regulated and perfused by the autonomous movement of the capillary vessels of the microcirculation part without synchronizing with the heartbeat, so that the microcirculation is compared with the 'second heart' of the human body in medicine. The function of microcirculation is mainly three-fold: the site of the substance exchange, blood transports oxygen, nutrients, hormones, water, etc. to the tissues, carrying away carbon dioxide and metabolites. The microcirculation is the only place where these substances are exchanged; communicating all tissue cells of the whole body; regulating blood flow and blood volume, the microcirculation has extremely large number of blood vessels and large capacity, and is a large blood storage pool. By changing the blood volume of the blood bank, the whole body circulation blood volume and the venous return blood volume can be adjusted. Once the microcirculation blood vessels of the whole body are opened greatly due to some reasons, a large amount of blood is accumulated in the microcirculation, so that the circulating blood volume and the return blood volume are reduced, and the blood pressure is reduced. If the correction is not carried out in time, serious results are necessarily caused. Microcirculation disturbance is common in middle-aged and elderly people, and when microcirculation is disturbed, microcirculation blood vessels deform and block the blood vessels, so that organ tissues, cell ischemia, hypoxic cell necrosis and pathological changes are caused. Microcirculation is smooth and all diseases are not born, and microcirculation disturbance is the source of all diseases. Because the capillary vessels are very long and impurities such as cholesterol, alcohol, nicotine, drug residues, chemical residues and the like are always turbid in blood, the blood vessel walls are thickened, the blood vessels are often blocked sometimes, the blood runs unsmoothly, cells of the whole body cannot be metabolized in time to weaken the functions of the cells, and diseases are generated after the blood vessels grow old. Microcirculation can be the primary or secondary responding organ for many pathological processes and diseases, and thus microcirculation disturbance occurs. Microcirculatory disturbance refers to the functional or organic disturbance of the level of microvascular and microvascular blood flow, which results in disturbance of the perfusion of the microcirculatory blood. Microcirculation disturbance finally causes blood cells to gather, blood flow is slow, blood is concentrated, blood viscosity is increased, thrombus is easy to form, or tissue cells are subjected to ischemia and hypoxia to cause pathological changes. Generally, microcirculation disturbance is unconsciously generated and possibly has no obvious symptoms for a certain period of time and is in a latent period, and the main detection means for discovering the microcirculation disturbance is the living observation by a computer microcirculation microscopic television system, which can not be replaced by general X-ray, electrocardiogram and B-ultrasonic.

Ovary, anatomical name. Located in the female pelvic cavity, are paired parenchymal organs. Belongs to female gonad, and is in flat oval shape, and comprises an inner side surface, an outer side surface, an anterior edge, a posterior edge, an upper end and a lower end. The lateral surface is pasted on the side wall of the pelvic cavity and is positioned at the included angle between the internal iliac part and the external artery starting part, and the medial surface faces the uterus; the upper end is connected with the pelvic cavity wall by an ovary suspensory ligament, and the lower end is connected with the uterus by an ovary inherent ligament; the posterior margin is free and the anterior margin has mesenteric attachments with vascular, lymphatic, and neural access. Its size and shape changes with age: in the young girl stage, the surface is smooth; after puberty, due to repeated ovulation, scars and unevenness are formed on the surface; the ovary in the sexual maturity stage is the largest, the length is 2.5-5.0 cm, the width is 1.5-3.0 cm, and the thickness is 0.6-1.5 cm. After menopause, the volume is significantly reduced, while in older women, the length, width and thickness are all only about 0.5 cm. Its main functions are to produce and discharge egg cells, and to secrete sex hormones to promote and maintain the development of female sexual characteristics. Generally, the left and right ovaries alternately discharge mature ova monthly.

Poor ovarian function can affect female hormone secretion, sexual function, skin quality, skin color and female three-dimensional posture, so that the face is yellow, the body is bloated, the vagina is dry, and the woman can enter the climacteric period in advance, namely, the aging comes. When the female reaches the age of 35-45 years, the ovaries begin to shrink gradually, and after menopause, the ovaries can gradually shrink to 1/2 in original volume. As the ovaries are ovulated frequently, the follicles collapse and are replaced by connective tissue, hardening progressively in nature. Therefore, in the aspect of life habits, female friends need to keep on drinking milk frequently, ingest food such as fish and shrimps, exercise body frequently, strengthen physique, and particularly pay attention to reduce passive smoking in public places and families, so that the harm to female health caused by early menopause is avoided. The ovary is well maintained, the facial skin can be fine and smooth, the white and transparent red skin can be obtained, and the toughness and the elasticity can be kept for a long time; promoting reproduction and body health, regulating and secreting female hormone, and improving the sexual life quality; the chest is full, compact and mellow.

With the continuous change of life rhythm and social environment, more and more women have poor premature ovarian function, so that premature ovarian failure occurs in many women who are not aged 30 years, which is undoubtedly a heavy strike for women who are not born. It is because of this realization that early prevention of potentially harmful factors is needed to reduce the incidence of ovarian functional senescence. Whether the female ovary function is normal can be known by referring to the following indexes: one is the ovulation function of the ovaries. Many women develop poor follicular function at a young age, mainly manifested by either excessive or too little ovulation per month. When the ovulation number increases every month, irregular menstruation can be caused to occur to the female, so that corresponding polycystic ovary syndrome occurs, the blood sugar, the blood pressure and the like of the female are changed, and the infertility probability of the female is increased. Therefore, for women with menstruation, it is important to monitor follicles when the menstruation is not good, and especially for women with abnormal number of follicles, treatment should be performed after consultation in hospital so as not to cause infertility symptoms in the childbearing age. Second, there are 6 sex hormones, which are closely related to the secretion of ovaries, and are generally examined for their ovarian function. These 6 hormones, follicle-forming hormone, luteinizing hormone, estradiol, progesterone, testosterone and prolactin, respectively, essentially cover the function of the ovarian secretion and thus the ovary can be essentially known by examination of these 6 hormones. Thirdly, the result of the B-ultrasonic report not only reflects the appearance of the ovary, but also determines whether there are any ovarian cysts, especially the more common endopathy and malignant cysts, and the appearance of these cysts can cause problems in the function of the ovary, so that the B-ultrasonic must be used to perform a one-by-one investigation. The ovary can be examined by B-ultrasonic, other cysts can be found by B-ultrasonic, and operation treatment, including drug treatment and the like, is needed when necessary.

Premature ovarian failure refers to the condition that women have a natural menstrual cycle, but before age 45, the atrophic menstrual flow of ovaries decreases, the menstrual period shortens, and the menstrual cycle increases until amenorrhea continues. The etiology may be infection, iatrogenic premature ovarian failure, idiopathic premature ovarian failure, immune factors and the like. Meanwhile, the second sexual characteristics are clinically reduced, and climacteric symptoms such as face fever, vexation, irritability and the like are caused; common cold is easy to occur at ordinary times, and the level of follicle stimulating hormone rises to more than 40 units, which is equivalent to the level of postmenopausal women; while the blood estradiol levels were significantly lower. The female genitalia is obviously atrophied in gynecological examination, and the vaginal mucosa is thin and congested. Ovarian biopsy is performed by laparotomy, ovarian atrophy can be seen, fibrous tissues are found in ovarian cortex under a microscope, and all levels of follicles such as primordial follicles are not visible.

The causes of premature ovarian failure include the following, 1. infection: the virus such as herpes simplex virus, mumps virus, etc. can cause ovarian inflammation or immune ovarian damage to cause premature ovarian failure. The decline of the ovarian function is a progressive process, and most patients show scanty menstruation or menstrual disorder before premature ovarian failure, and can show perimenopausal symptoms such as hot flushes, sweating, vexation, amnesia and the like. Women have obvious aging and dry skin, and are easy to have osteoporosis. 2. Iatrogenic premature ovarian failure. Premature ovarian failure can be caused by hypofunction of tissues such as ovaries caused by cutting two or one ovaries before the age of 40. It has been thought that after excision of one ovary, the contralateral ovary maintains normal endocrine function. In recent years, it has been found that after one-sided ovariectomy, the hormone secretion from the ovaries decreases, and the chances of osteoporosis and climacteric symptoms increase. In addition, invasive surgical procedures, such as repeated artificial abortion, should be avoided as much as possible. 3. Idiopathic premature ovarian failure. Is a secondary amenorrhea without clear pathogenic factors and is the most important type of premature ovarian failure. The disease is usually developed at the birth age, gradual or progressive scanty menstruation appears clinically, then amenorrhea is accompanied with climacteric symptoms such as hot flashes, dysphoria and the like, and internal and external reproductive organs are in an atrophy state. 4. Immune factors: many immune diseases such as thyroiditis can be associated with premature ovarian failure. Premature ovarian failure is generally considered to be an autoimmune disease, and may be immune oophoritis of the organism to the self ovarian tissue caused by virus infection. Autoimmune diseases are caused by the concurrent occurrence of autoimmune phenomena or the simultaneous occurrence of more than one disease, which is shown in the polyglandular exhaustion syndrome. Lymphocyte infiltration is seen in ovarian biopsies due to the presence of an anti-ovarian antibody in the serum of ovarian autoimmune subjects. It is caused by the influence of operation and radiotherapy on the blood circulation of ovary. This is caused by congenital deficiency of the follicles or by hyperstimulation of gonadotropins accelerating follicular atresia. 5. Modern people have an increased infertility rate, and some women are forced to use ovulation-promoting methods to increase the probability of pregnancy, but the ovarian killing power is very large if the practice is excessive. 6. Excessive weight loss causes the body fat to be reduced rapidly, the level of estrogen in the body can be influenced when the fat ratio is too low, because the main raw material for synthesizing the estrogen is fat, the body fat is insufficient, the estrogen is reduced, the menstrual disorder can be caused, even amenorrhea can occur, the ovulation function of ovaries can be inhibited instead of normal amenorrhea, the premature ovarian failure can be easily caused, and if the treatment is not timely, the infertility can be even caused. Premature ovarian failure can exacerbate menstrual disorders, thus creating a vicious circle. 7. Modern women are in intense competition, and due to excessive mental stress, vegetative nerve functional disturbance can be caused in the past, and endocrine regulation of a human body is influenced, so that the ovarian function is prematurely declined, the secretion of estrogen is reduced, and the menopause comes in advance. 8. Smoking, drinking and other bad habits can also lead to premature ovarian failure, as nicotine in cigarettes and alcohol in wine interfere with normal menstruation and lead to menstrual disorder. Clinically, amenorrhea, blood FSH and LH are remarkably increased, blood E2 extremely falls and ovary tissue biopsy primordial-free follicles can be diagnosed definitely. The clinical manifestations of premature ovarian failure mainly include the following aspects, 1. premature ovarian failure patients are easy to have secondary infertility caused by gonad development, and the menstruation gradually becomes sparse after years until amenorrhea. 2. Premature ovarian failure patients are easy to cause gonad undevelopment, primary amenorrhea, hypogonadism with delayed onset of tide or irregular menstruation, and dysmenorrhea. 3. Premature ovarian failure can cause atrophy and ptosis of breasts, loose and rough skin, tension, dreaminess, suspiciousness, palpitation, osteoporosis, arthralgia, inflammation of reproductive organs, uterine ptosis, urinary incontinence, constipation, pox and color spots. 4. Premature ovarian failure patients are easy to cause anovulation and have ovulation, and the typical POF has hot flashes, hypogonadism manifestations, such as night sweat, constipation, alopecia, vaginal dryness, sexual life pain, decreased libido, hypothyroidism, urinary system infection, weight gain, anxiety, suspiciousness, etc.

According to the above, the female skin can be improved by improving the female ovarian function. Such as yellowing of the face, dry skin, loose and rough skin, etc.

Hemoglobin (Hb, HGB), a specific protein for transporting oxygen in red blood cells, is a protein that gives blood a red color, and is composed of globin and heme, and the globin portion thereof is a tetramer composed of two pairs of different globin chains (α chain and β chain). Currently, international systems are adopted in various systems, based on how many grams of hemoglobin per liter (one thousand milliliters) of blood is. The hemoglobin is similar to the use value of red blood cells, and the increase and decrease of the hemoglobin can be referred to the clinical significance of the increase and decrease of the red blood cells. The general reference range (instrumental method) of human Hb is 120-160 g/L for men, 110-150 g/L for women, 165-195 g/L for newborns and 120-140 g/L for children, and the hemoglobin content of children gradually decreases with age and approaches to adults.

Hb molecular structure: each 1Hb molecule consists of 1 globin and 4 heme (also known as ferriprotoporphyrin). Each heme group is composed of 4 pyrrole groups to form a ring with an iron atom at the center. Each globin has 4 polypeptide chains, each polypeptide chain being linked to 1 heme to form a monomer or subunit of Hb. Hb is a tetramer of 4 monomers. The composition of the polypeptide chains of the globin of different Hb molecules differs. The polypeptide chain of adult hb (hba) is 2 α and 2 β chains, an α 2 β 2 structure. Fetal hb (hbf) is 2 alpha chains and 2 gamma chains, being an alpha 2 gamma 2 structure. HbF is replaced by HbFA shortly after birth. The order of the amino acids in the polypeptide chain is well understood. Each alpha chain contains 141 amino acid residues and each beta chain contains 146 amino acid residues. The Fe2+ of heme is linked to a group of amino acid residues in the polypeptide chain, which, if substituted with other amino acids, or their adjacent amino acids are altered, affect Hb function. It can be seen that the protein structure and function are closely related.

Clinical significance of hemoglobin: the clinical significance of hemoglobin elevation and lowering is substantially similar to that of red blood cell count, but hemoglobin better reflects the degree of anemia. There are the following conditions for hemoglobin increase: physiological increase: seen in plateau residents, fetuses and newborns, severe activities, fear, cold water bath and the like; pathological increase: severe congenital and acquired cardiopulmonary diseases and vascular malformations such as French tetrad, cyanotic congenital heart disease, obstructive pulmonary emphysema, pulmonary heart disease, pulmonary arterial fistula or pulmonary venous fistula, and abnormal hemoglobinopathy with low oxygen carrying capacity; it is also found in some tumors or kidney diseases, such as renal cancer, hepatocellular carcinoma, nephroblastoma, hydronephrosis, polycystic kidney, etc. Hemoglobin reduction is seen in the following cases: physiological reduction: the relative deficiency of hematopoietic system caused by rapid growth and development mainly in children from 3 months to 15 years old is generally 10% -20% lower than that of normal people. The middle and late gestation period can result in dilution of blood due to increased blood volume, and the elderly can result in decreased red blood cell and hemoglobin content due to gradually decreased bone marrow hematopoiesis. The reasons for the pathological reduction of hemoglobin are mainly as follows: bone marrow hematopoietic failure, such as aplastic anemia, anemia associated with myelofibrosis; anemia due to hematopoietic deficiency or impaired utilization, such as iron deficiency anemia, and megaloblastic anemia due to folic acid and vitamin B12 deficiency; anemia caused by excessive destruction of erythrocytes due to genetic defects of erythrocyte membranes, enzymes or external factors, such as hereditary spherocytosis, marine anemia, paroxysmal nocturnal hemoglobinuria, abnormal hemoglobinopathy, immune hemolytic anemia, hemolytic anemia caused by major surgery of cardiac extracorporeal circulation or certain biological and chemical factors, and anemia caused by certain acute or chronic blood loss.

Arteriosclerosis is a non-inflammatory lesion of an artery, and can thicken and harden the wall of an artery, lose elasticity and narrow a lumen. Arteriosclerosis is a vascular disease which appears with age, and the rule is that the arteriosclerosis usually occurs in teenagers and aggravates and attacks the middle-aged and elderly people. Aortic sclerosis is a common type of arteriosclerosis. There are three main types of arteriosclerosis: hardening of small arteries; hardening the middle layer of artery; ③ atherosclerosis. The disease mainly affects aorta, coronary artery, cerebral artery and renal artery, can cause the narrowing and even the occlusion of the lumen of the above arteries, and can cause aortic dissection and abdominal aneurysm; causing a blood supply disorder in the organs supplied by the organ, resulting in ischemic pathological changes in these organs.

The most important causes of arteriosclerosis are hypertension, hyperlipidemia and smoking. Other conditions such as obesity, diabetes, hypokinesia, stress, advanced age, family history, and irritable bowel syndrome can cause arteriosclerosis. In terms of clinical manifestations of arteriosclerosis, most of them have no specific symptoms. Widening of the turbid aortic region behind the sternum stem can be found during percussion; the second heart sound in the aortic valve area is high and has metallic tone and systolic murmur. Systolic blood pressure is high, pulse pressure is widened, and radial artery palpation can be similar to pulse promotion. The aortic nodes are protruded to the left and upward, the aorta is expanded and twisted, and the calcareous deposition shadow in the flaky or arc plaque can be seen sometimes. Most lesions occur in the posterior wall of the aorta and at the branch openings thereof. The abdominal aorta is most diseased, followed by the descending aorta and aortic arch, and again the ascending aorta. In severe cases, plaque ruptures and forms an atheromatous ulcer, which may have mural thrombosis on its surface. In some cases, the tunica media SMC shrinks, the elastic plate is broken, the local pipe wall becomes weak, and the pipe wall bulges outwards under the action of blood pressure to form aortic aneurysm. Such aneurysms are found primarily in the abdominal aorta. Occasionally, the aneurysm ruptures, causing fatal massive hemorrhage. Sometimes a dissecting aneurysm may occur. In some cases, the aortic intima at the root is seriously diseased, and the aortic valve is affected, so that the valve is thickened, hardened and even calcified to form aortic valvulopathy.

In the examination of arteriosclerosis, blood vessels should be evaluated from both functional and structural aspects: function is the elastic condition of the blood vessel; the structure is a stenosis of a blood vessel. A recent method for non-invasive examination of arteriosclerosis is available that can measure two indicators simultaneously: ABI ankle index, PWV pulse wave velocity. 1. Laboratory examination: sensitive and specific early-stage laboratory diagnostic methods are lacking. The patients have lipid metabolism disorder, which is mainly manifested by increased total cholesterol, increased LDL cholesterol, decreased HDL cholesterol, increased triglyceride, increased lipoprotein, increased apolipoprotein B, decreased apolipoprotein A, increased lipoprotein (alpha) and abnormal lipoprotein electrophoresis pattern, and more than 90% of patients show type II or type IV hyperlipoproteinemia. 2. Examination of hemorheology: it usually indicates an increased blood viscosity. Platelet activity may be increased. X-ray examination: the corresponding part of the aorta is enlarged as can be seen in X-ray examination; aortic angiography can reveal spindle or sac-like aneurysms. The two-dimensional ultrasonic imaging, computerized X-ray tomography and magnetic resonance tomography can display the expansion of the tumor-like aorta. An aortic aneurysm, once ruptured, can be rapidly fatal. Atherosclerosis can also form a dissecting aneurysm, but is less common. 4. Doppler ultrasound examination. 5. Intravascular ultrasound and angioscopy: is a method for directly observing atherosclerotic lesions in the arterial lumen. 6. And others: echocardiography, electrocardiography and stress tests thereof. In the diagnosis of arteriosclerosis, the diagnosis can be made according to the etiology, clinical manifestations and imaging examinations. Aortic changes and aortic aneurysms caused by aortic atherosclerosis must be identified with syphilitic aortic inflammation and aortic aneurysms and mediastinal tumors. The complications of arteriosclerosis are mainly the following, 1. abdominal aortic aneurysm: the pulsation mass of the abdomen is usually found during physical examination, while the corresponding parts on the abdominal wall can hear noise and the pulsation of the femoral artery can be weakened. 2. Thoracic aortic aneurysm: can cause chest pain, dyspnea, dysphagia, hemoptysis, paralysis of vocal cords due to the compression of recurrent laryngeal nerves, trachea displacement or obstruction, and compression of superior vena cava and pulmonary artery.

The treatment of arteriosclerosis includes the following aspects of 1. expanding blood vessels and relieving vascular dyskinesia, and the selectable medicines include isosorbide mononitrate, nitrodipine sustained-release tablets, diltiazem and the like. 2. Regulating blood lipid, and regulating blood lipid when blood lipid is higher than normal on the basis of reasonable diet and proper amount of exercise. (1) The triglyceride-lowering drugs fenofibrate, atorvastatin and gemfibrozil. (2) The cholesterol-lowering drugs include simvastatin, fluvastatin and pravastatin. 3. The medicine for resisting platelet adhesion and aggregation can prevent thrombosis and the occurrence and development of vascular occlusion diseases. The commonly used medicines are: enteric aspirin, ticlopidine, and the like. 4. Thrombolytic and anticoagulant drugs, for those with lumen stenosis or obstruction due to intra-arterial thrombosis, can be used, such as urokinase, recombinant tissue plasminogen activator, heparin, etc. In addition to the above-described treatment methods for arteriosclerosis, interventional procedures including surgical procedures such as recanalization, re-or bypass grafting of stenotic or occluded blood vessels, particularly coronary, renal and limb arteries, may be used to restore arterial blood supply. In the prevention of arteriosclerosis, the occurrence of atherosclerosis should be actively prevented, i.e., primary prevention, in the first place. If it has occurred, the treatment should be active, preventing the development of the lesion and striving for its reversal, i.e. secondary prevention. The patients with the complications are treated in time to prevent the patients from worsening, and the life of the patients is prolonged, namely the third-level prevention. 1. The subjective motility of the patient is exerted to cooperate with the treatment, the disease condition can be controlled by the prevention and treatment, the pathological changes can be partially subsided, the patient can maintain certain living and working capacity, and the pathological changes can promote the formation of arterial collateral circulation to improve the disease condition. It is therefore of great importance to convince patients to take long-term preventive measures. 2. Reasonable diet, even if the blood fat is not increased in 40 years old, the frequent eating of excessive animal fat and vegetable oil containing saturated fatty acid, such as: fat meat, lard, bone marrow, butter and its products, coconut oil, cocoa butter, etc.; avoid overeating foods with higher cholesterol, such as: internal organs such as liver, brain, kidney and lung, squid, cuttlefish, roe, shrimp roe, crab roe, egg yolk, etc. If blood lipid is continuously increased, low-cholesterol and low-animal fat foods should be eaten, such as: various lean meat, chicken, duck, fish meat, protein, bean products, etc. 3. The traditional Chinese medicine composition has the advantages of being suitable for physical labor and physical activities, participating in certain physical labor and physical activities, being beneficial to preventing obesity, exercising the function of a circulatory system and adjusting blood lipid metabolism, and being an active measure for preventing the disease. Physical activity should be regulated according to original physical condition, original physical activity habit and heart function state, in order not to increase too much heart burden and not to cause uncomfortable feeling as principle. The physical activities can be progressive, so that the people are not suitable for doing violent activities reluctantly, and the old advocates walking, doing health gymnastics, playing taijiquan and the like. 4. Work and life are reasonably arranged, life is regular, optimistic and pleasant emotion is kept, excessive fatigue and emotion excitement are avoided, attention is paid to the combination of overstrain and ease, and sufficient sleep is guaranteed. 5. The smoking cessation limit advocates no smoking, no strong spirit or large amount of alcohol (small amount of low concentration alcohol can increase blood HDL). 6. Actively treating diseases related to the disease, such as hypertension, adiposity, hyperlipoidemia, gout, diabetes, liver disease, nephrotic syndrome, related endocrinopathy and the like.

The Chinese nutritional society dietary guidelines of women and children revise expert committees, Chinese nutritional society dietary guidelines of women and children formulated by the Chinese nutritional society are formulated aiming at the nutritional characteristics of pregnant women and nursing mothers on the basis of the dietary guidelines of general population. Version 2007 contains part 4 of the dietary guidelines for pre-pregnant women, intermediate and terminal pregnant women, and lactating women. In order to improve the quality of the birth population in China and reduce the incidence of birth defects caused by folic acid deficiency, iron deficiency, iodine deficiency and the like. On the basis of the 1997 pregnant woman dietary guidelines, dietary guidelines for women of childbearing age are added, and the guidance that special diet and healthy lifestyle guidance should be accepted 3-6 months before planning pregnancy is provided, so that the nutrition of the pregnant woman is adjusted, the health condition and the living habits are improved, the pregnant woman reaches the optimal state as far as possible, and the success of pregnancy is facilitated. The pre-pregnant woman dietary guidelines included 4 more foods rich in folate or supplemented with folate; the food rich in iron is often eaten; ensuring that the iodine-added salt is ingested and properly increasing the ingestion of marine products: stop smoking and abstain from drinking. For women in early pregnancy, aiming at the influence of the early pregnancy reaction on food and nutrition intake, the diet is emphasized to be rich in nutrition, easy to digest, light and palatable, and the aim is to enable the early pregnancy women to take more food and nutrition as possible. The contents of the diet guide comprise the following 5 foods which are light and palatable; eating too little food; ensuring ingestion of sufficient carbohydrate-rich food; increased intake of folate-rich food and supplementation with folate; stop smoking and abstain from drinking. For pregnant women in middle and late stages, the nutrient solution aims at the rapid growth and development of fetus and maternal reproductive organs and energy and nutrient reserve which are necessary for postpartum lactation of the maternal. The intake of protein, energy, calcium, iron, iodine and other nutrients is properly increased. The following 5 dietary guidelines are provided for women in the middle and late stages of pregnancy, which properly increase the intake of fish, poultry, eggs, lean meat and seafood; properly increasing the intake of milk; the food rich in iron is often eaten; proper physical activity is performed to maintain proper weight increase; abstain from smoking and drinking, and eat less irritant food. Lactating women (lactating mothers) need to secrete milk to feed babies, and gradually compensate nutritional reserves lost during pregnancy and childbirth to promote recovery of organs and system functions. More importantly, the nutrition deficiency also affects the health of the mother, reduces the milk secretion, reduces the milk quality and affects the growth and development of the baby. Therefore, the diet should be arranged reasonably according to the physiological characteristics of the lactation period and the requirement of milk secretion, so as to ensure sufficient nutrition supply. The following 5 dietary guidelines for lactating women were emphasized to increase the intake of fish, poultry, eggs, lean meat and seafood; properly increase the milk, and drink more soup; the food in the puerperium is various and not excessive; smoking and drinking are avoided, and thick tea and coffee are avoided; scientific exercise and exercise, and recovery of healthy weight. According to the above general guidelines, the intake and supplementation of iron in sufficient quantities in pregnant women, parturients, lactating mothers, fetuses and even young children is of paramount importance for improving and enhancing body functions.

The technical solution of the present invention has been proved to exhibit one or more unexpected advantageous effects by a number of experiments.

Detailed Description

The present invention will be further described by the following examples, however, the scope of the present invention is not limited to the following examples. It will be understood by those skilled in the art that various changes and modifications may be made to the invention without departing from the spirit and scope of the invention. The present invention has been described generally and/or specifically with respect to materials used in testing and testing methods. Although many materials and methods of operation are known in the art for the purpose of carrying out the invention, the invention is nevertheless described herein in as detail as possible. The formulation below is expressed in parts by weight for the preparation of the composition, with a total dosage of at least 10 kg per batch, and in the specific formulation form, each unit formulation contains 100mg hemin.

Example 1: preparation of the composition

Prescription: hemin: 100 parts by weight of a water-soluble polymer,

diluent (starch): 300 parts by weight of a solvent, and a solvent,

phospholipid (soybean): 7.5 parts by weight.

The preparation method comprises the following steps: pre-pulverizing hemin into fine powder capable of passing through 100 mesh sieve; dissolving phospholipid in ethanol to obtain 22% solution; spraying phospholipid solution into fluidized hemin fine powder in fluidizing equipment (fluidized bed granulator) at 33 deg.C, and further fluidizing to remove ethanol; adding 25 parts by weight of diluent, uniformly mixing, and pressing the materials into a sheet-shaped object by using an extruder; freezing the sheet at-18 deg.C for 28 hr; crushing the sheet, adding the rest of diluent, uniformly mixing, and continuously crushing into fine powder which can pass through a 60-mesh sieve to obtain a composition;

further, half amount of the finely powdered composition is prepared in the form of a preparation (capsule).

Example 2: preparation of the composition

Prescription: hemin: 100 parts by weight of a water-soluble polymer,

diluent (sucrose): 50 parts by weight of a water-soluble polymer,

phospholipid (soybean): 25 parts by weight.

The preparation method comprises the following steps: pre-pulverizing hemin into fine powder capable of passing through 100 mesh sieve; dissolving phospholipid in ethanol to obtain 20% solution; spraying phospholipid solution into fluidized hemin fine powder in a fluidizing device (fluidized bed granulator) at 35 deg.C, and continuously fluidizing to remove ethanol; adding 30 parts by weight of diluent, uniformly mixing, and pressing the materials into a sheet-shaped object by using an extruder; freezing the sheet at-20 deg.C for 24 hr; crushing the sheet, adding the rest of diluent, uniformly mixing, and continuously crushing into fine powder which can pass through a 60-mesh sieve to obtain a composition;

further, half amount of the finely powdered composition is made into a preparation form (tablet).

Example 3: preparation of the composition

Prescription: hemin: 100 parts by weight of a water-soluble polymer,

diluent (lactose): 1200 parts by weight of a water-soluble polymer,

phospholipid (soybean): 1 part by weight.

The preparation method comprises the following steps: pre-pulverizing hemin into fine powder capable of passing through 100 mesh sieve; dissolving phospholipid in ethanol to obtain 25% solution; spraying phospholipid solution into fluidized hemin fine powder in fluidizing equipment (fluidized bed granulator) at 30 deg.C, and further fluidizing to remove ethanol; adding 20 parts by weight of diluent, uniformly mixing, and pressing the materials into a sheet-shaped object by using an extruder; freezing the sheet at-15 deg.C for 30 hr; crushing the sheet, adding the rest of diluent, uniformly mixing, and continuously crushing into fine powder which can pass through a 60-mesh sieve to obtain a composition;

further, half amount of the composition in the form of a fine powder is prepared into a preparation form (soft capsule).

Example 4: preparation of the composition

Prescription: hemin: 100 parts by weight of a water-soluble polymer,

diluent (microcrystalline cellulose): 750 parts by weight of a curing agent,

phospholipid (egg yolk): 5 parts by weight.

The preparation method comprises the following steps: pre-pulverizing hemin into fine powder capable of passing through 100 mesh sieve; dissolving phospholipid in ethanol to obtain 21% solution; spraying phospholipid solution into fluidized hemin fine powder in a fluidizing device (fluidized bed granulator) at 34 deg.C, and further fluidizing to remove ethanol; adding 22 parts by weight of diluent, uniformly mixing, and pressing the materials into a sheet-shaped object by using an extruder; freezing the sheet at-19 deg.C for 25 hr; crushing the sheet, adding the rest of diluent, uniformly mixing, and continuously crushing into fine powder which can pass through a 60-mesh sieve to obtain a composition;

further, half amount of the finely powdered composition is made into a preparation form (granules).

Example 5: preparation of the composition

Prescription: hemin: 100 parts by weight of a water-soluble polymer,

diluent (calcium hydrogen phosphate): 100 parts by weight of a water-soluble polymer,

phospholipid (egg yolk): 15 parts by weight.

The preparation method comprises the following steps: pre-pulverizing hemin into fine powder capable of passing through 100 mesh sieve; dissolving phospholipid in ethanol to obtain 24% solution; spraying phospholipid solution into fluidized hemin fine powder in fluidization equipment (fluidized bed granulator) at 31 deg.C, and further fluidizing to remove ethanol; adding 28 parts by weight of diluent, uniformly mixing, and pressing the materials into a sheet-shaped object by using an extruder; freezing the sheet at-16 deg.C for 29 hr; crushing the sheet, adding the rest of diluent, uniformly mixing, and continuously crushing into fine powder which can pass through a 60-mesh sieve to obtain a composition;

further, half of the amount of the finely powdered composition is prepared in the form of a preparation (dry suspension).

Example 6: preparation of the composition

Prescription: hemin: 100 parts by weight of a water-soluble polymer,

diluent (starch): 100 parts by weight of a water-soluble polymer,

phospholipid (soybean): 5 parts by weight.

The preparation method comprises the following steps: pre-pulverizing hemin into fine powder capable of passing through 100 mesh sieve; dissolving phospholipid in ethanol to obtain 22% solution; spraying phospholipid solution into fluidized hemin fine powder in fluidizing equipment (fluidized bed granulator) at 33 deg.C, and further fluidizing to remove ethanol; adding 24 parts by weight of diluent, uniformly mixing, and pressing the materials into a sheet-shaped object by using an extruder; freezing the sheet at-17 deg.C for 26 hr; crushing the sheet, adding the rest of diluent, uniformly mixing, and continuously crushing into fine powder which can pass through a 60-mesh sieve to obtain a composition;

further, half amount of the finely powdered composition is made into a preparation form (tablet).

Example 7: preparation of the composition

Prescription: hemin: 100 parts by weight of a water-soluble polymer,

diluent (starch): 500 parts by weight of a water-soluble polymer,

phospholipid (soybean): 10 parts by weight.

The preparation method comprises the following steps: pre-pulverizing hemin into fine powder capable of passing through 100 mesh sieve; dissolving phospholipid in ethanol to obtain 23% solution; spraying phospholipid solution into fluidized hemin fine powder in 32 deg.C fluidizing equipment (fluidized bed granulator), and further fluidizing to remove ethanol; adding 26 parts by weight of diluent, uniformly mixing, and pressing the materials into a sheet-shaped object by using an extruder; freezing the sheet at-18 deg.C for 28 hr; crushing the sheet, adding the rest of diluent, uniformly mixing, and continuously crushing into fine powder which can pass through a 60-mesh sieve to obtain a composition;

further, half amount of the finely powdered composition is prepared in the form of a preparation (capsule).

Example 8: preparation of the composition

Reference examples 1 to 7, except that they were prepared (without freezing) as follows: pre-pulverizing hemin into fine powder capable of passing through 100 mesh sieve; dissolving phospholipid in ethanol to obtain solution with corresponding concentration; spraying phospholipid solution into fluidized hemin fine powder in fluidization equipment (fluidized bed granulator) at corresponding temperature, and continuously fluidizing to remove ethanol; adding a corresponding amount of diluent, uniformly mixing, and pressing the materials into a sheet-shaped object by using an extruder; crushing the sheet, adding the rest of diluent, uniformly mixing, and continuously crushing into fine powder which can pass through a 60-mesh sieve to obtain a composition; further, half of the amount of the finely powdered composition was prepared into a corresponding formulation form. 7 compositions and preparations were obtained.

Example 9: preparation of the composition

Reference examples 1 to 7, except that they were prepared as follows (without tableting): pre-pulverizing hemin into fine powder capable of passing through 100 mesh sieve; dissolving phospholipid in ethanol to obtain solution with corresponding concentration; spraying phospholipid solution into fluidized hemin fine powder in fluidization equipment (fluidized bed granulator) at corresponding temperature, and continuously fluidizing to remove ethanol; adding a corresponding amount of diluent, uniformly mixing, and freezing the mixture at a corresponding temperature for a corresponding time; adding the rest of the diluent and mixing uniformly to obtain a composition; further, half of the amount of the finely powdered composition was prepared into a corresponding formulation form. 7 compositions and preparations were obtained.

Example 10: preparation of the composition

Reference examples 1 to 7, except that no phospholipids were added and prepared as follows (no phospholipids added): pre-pulverizing hemin into fine powder capable of passing through 100 mesh sieve; spraying the ethanol solution into the fine hemin powder in a fluidized state in a fluidizing device (such as a fluidized bed granulator) at a corresponding temperature, and continuously fluidizing to remove ethanol (the powder is granulated as in examples 1-7); adding a corresponding amount of diluent, uniformly mixing, and pressing the materials into a sheet-shaped object by using an extruder; freezing the sheet at the corresponding temperature for the corresponding time; crushing the sheet, adding the rest of diluent, uniformly mixing, and continuously crushing into fine powder which can pass through a 60-mesh sieve to obtain a composition; further, half of the amount of the finely powdered composition was prepared into a corresponding formulation form. 7 compositions and preparations were obtained. 7 compositions and preparations were obtained.

Test example 1: hemin composition for treating iron deficiency anemia

1. Subject: male with hemoglobin (Hb) as a clinical diagnosis standard for iron deficiency anemia<120g/L for female<110 g/L; red Blood Cells (RBC), male<400×10¹⁰L, female<350×10¹⁰L; serum Ferritin (SF), male sex<15 ug/L for women<12 mu g/L; serum ferrum (SI)<11 mu mol/L; total Iron Binding Capacity (TIBC)>64 mu mol/L; wherein SF has a large value for iron deficiency, excessive storage amount of iron agent and the likeThe value is obtained. 38 anemia patients, 5 males and 33 females, age 17-61 years and average age 48.2 years are selected, and all patients are treated by ferrous sulfate and are not cured; before taking the medicine, the patient is asked for medical history, physical examination and blood system test.

2. The blood examination method comprises the following steps: hemoglobin is measured by a photoelectric colorimetry, red blood cells are measured by counting, and serum iron, ferritin and total iron binding force are measured by an enzyme labeling method.

3. Dosage and treatment course: the dosage is 3 g per day calculated by hemin, and the preparation is orally taken for 3 times, 1 month is a treatment course, and all patients take a treatment course. Treatment was with the composition of example 1.

4. The curative effect is divided into obvious effect, gynecological conversion and ineffective effect, the clinical symptoms are obviously improved (dizziness, hypodynamia disappears, and the complexion is ruddy), at least 4 of 5 blood indexes are greatly improved (the hemoglobin is increased by more than 20g/L, and the red cell count is increased by 50 × 10¹⁰More than one liter, the ferritin is increased by more than 10 mu g/L, the serum iron is increased by more than 4 mu mol/L, and the total iron binding force is reduced by more than 10 mu mol/L); improvement: the clinical symptoms are improved, at least 2 of the 5 blood indexes are greatly improved, and other blood indexes are also improved; and (4) invalidation: those who did not achieve the effect and who had good conversion criteria were all listed as being ineffective.

5. As a result: comparison of subjective symptoms before and after administration to all patients: 33 cases of dizziness, 36 cases of hypodynamia, 21 cases of pale complexion and 16 cases of anorexia before administration; after treatment, there are 1 case of dizziness, 2 cases of hypodynamia, 0 case of pale complexion and 0 case of anorexia. The comparison of the mean values of the various blood indicators before and after treatment (mean ± SD, n-38) is shown in the following table:

index (I)	Criteria for anemia	Before taking medicine	After taking the medicine	Mean value difference	p value
						Hemoglobin, Hb (g/L)	<120 or<110	88.2±10.7	119.4±10.7	31.2	<0.001
Red blood cells, RBC (10)10/L)	<400 or<350	292±33	413±51	121	<0.001
						Serum ferritin, SF (μ g/L)	<15 or<12	9.2±1.3	16.4±3.8	7.2	<0.001
Serum iron, SI (μmol/L)	<11	8.6±2.2	14.1±2.6	5.5	<0.001
						Total iron binding force, TIBC (mol/L)	>64	73±14	52±9	-21	<0.001

Wherein, the p value is the comparison of each index before and after treatment, and has statistically significant difference.

According to statistics of the curative effect judgment standard, 29 persons with obvious effect account for 76.3 percent; improving 8 persons, accounting for 21.1 percent; invalid 1 person, accounting for 2.6%; among the significant patients, 14 patients were cured, the clinical symptoms disappeared and 5 blood indicators reached normal values. The gastrointestinal tract reaction is not seen in all the recipients, and the normal diet is not influenced.

Test example 2: pharmacodynamic study of hemin composition for treating anemia

In order to know the anti-anemia effect of hemin, a rat anemia model is established by combining iron deficiency anemia with blood loss anemia, and then hemin aqueous solution is orally administered to anemic rats. Hemoglobin (Hb), hematocrit (Hct) and free protoporphyrin (FEP) in erythrocytes were measured before and after the experiment. The method comprises the following steps: the material and the method are as follows: the animal is an SD male rat, and the weight of the animal is 110-130 g; animals were fed AOAC recommended low iron basal diet [ Williama S. official method of analysis of the association of official analytical chemists [ M ].14th edition, USA, 1984: 880], the iron content of the basal feed was 8 ppm. And (3) sample and grouping: examples 1, 6, 7 and examples 8, 9 each refer to the composition obtained in example 1, for a total of 5 powder mixtures, and the other group was fed with deionized water as a control. The method comprises the following steps: rats were fed a low iron basal diet in a non-iron environment with 25 drops of blood bleed per animal on alternate days. And when the average hemoglobin concentration of the animals is reduced to about 80g/L by the 3 rd week, measuring the hemoglobin and free protoporphyrin in red blood cells of the rats, weighing the weights, and finishing the establishment of the model. 60 anemic rats were randomly divided into 6 groups of 10 per group according to hemoglobin concentration and body weight, and 5 composition samples were individually subjected to intragastric administration (daily dose of each group was 5mg/kg body weight in terms of iron) 1 time a day. Meanwhile, a deionized water negative control group is arranged, and rats in each group continue to feed low-iron feed and drink deionized water. Each group of rats was raised in a single cage, and the body weight was weighed every 5 days in the test, and tail blood was taken to determine the hemoglobin concentration. After 4 weeks, when Hb of the control group was recovered to 95g/L, Hb, Hct, and FEP of the rat were measured. As a result: the weight average of the test precursor of each group of animals is in the range of 225-230 g, the weight average of the test body is in the range of 290-305 g, and the change before and after the test is not statistically different among the groups. Hb of each group before the test is in a range of 84-86 (g/L); compared with the groups before the test, the Hb increase value of the control group is 9.7 percent after the test, the Hb increase values of the groups of examples 1, 6 and 7 are in the range of 33-36 percent, and the Hb increase values of the groups of examples 8 and 9 are in the range of 22-23 percent and are obviously lower than those of the groups of examples 1, 6 and 7. Before the test, Hct of each group is within the range of 29-31%; compared with the control group before the test, the increase value of the Hct of each group after the test is 12.6 percent, the increase values of the Hct of the groups of examples 1, 6 and 7 are within the range of 31-33 percent, and the increase values of the Hct of the groups of examples 8 and 9 are within the range of 19-20 percent and are obviously lower than those of the groups of examples 1, 6 and 7. Before the test, each group of FEP is in the range of 14-15 mg/L; compared with the FEP before the test, the FEP reduction rate of the control group is 22.5 percent after the test, the FEP reduction rate of the examples 1, 6 and 7 is within the range of 39-41 percent, and the FEP reduction rate of the examples 8 and 9 is within the range of 31-32 percent. The above results show that the compositions of examples 1, 6 and 7 are significantly superior to the compositions of examples 8 and 9 in terms of the corresponding physiological index produced by the action with hemin.

Test example 3: hemin composition solubility study

Filling various powder compositions or raw material medicines into hollow capsules, wherein each capsule is 100mg calculated by hemin, a dissolving medium is 500ml by a dissolution tester according to a paddle method which is a second method of a 0931 dissolution and release determination method in the fourth part of 2015 of Chinese pharmacopoeia, each dissolving cup is put into a capsule, the capsule is stirred for 1 hour at 37 ℃, a solution is taken and filtered, and the absorbance is determined at the wavelength of 400 nm; dissolving hemin with ethanol, diluting to obtain control solution, measuring absorbance at 400nm wavelength, calculating hemin dissolution amount in the dissolution cup, and calculating hemin dissolution fraction according to theoretical hemin amount in each capsule. As a result: when the dissolving medium is water, the dissolution fraction of the raw material drug is 12.3%, the dissolution fraction of the total composition obtained in examples 8 to 10 is in the range of 11 to 14%, and the dissolution fraction of the total composition obtained in examples 1 to 7 is in the range of 43 to 47%; when the dissolution medium is 0.1M hydrochloric acid solution, the dissolution fraction of the raw material drug is 14.4%, the dissolution fraction of the total composition obtained in examples 8 to 10 is in the range of 15 to 17%, and the dissolution fraction of the total composition obtained in examples 1 to 7 is in the range of 54 to 59%; when the dissolution medium is 0.1M sodium hydroxide solution, the dissolution fraction of the crude drug is 13.1%, the dissolution fraction of the total composition obtained in examples 8 to 10 is in the range of 15 to 18%, and the dissolution fraction of the total composition obtained in examples 1 to 7 is in the range of 51 to 53%. The above results show that the compositions obtained by the process of the invention have significantly better dissolution properties, which provide sufficient evidence for efficient iron absorption by the compositions of the invention.

Test example 4: investigation of effects of improving qi and blood functions of human body and delaying aging of human body

As mentioned herein, qi deficiency manifests as exercise asthma, exercise palpitation, while blood deficiency manifests as sallow complexion, whitish complexion, dizziness, palpitation, poor sleep; the obvious appearance of aging is as follows: poor physical strength, easy insomnia, hearing loss, heavy taste, high blood pressure, alopecia, etc. In the experiment, the capsule obtained in the example 1 of the invention is used for inspecting the effect of the composition of the invention on improving the qi and blood functions of human bodies and delaying the aging of the human bodies.

268 subjects, 76 males and 192 females with an age of 36-62 years were included in the study, and among the 268 subjects, 184 subjects with qi deficiency, 237 subjects with blood deficiency and 202 subjects with aging were evaluated by observation, inquiry and complaint combination during the 1 month period before the start of the study. The subjects took the capsules of example 1 of the present invention (composition powder directly filled capsules) 3 g a day in 3 divided doses for 45 days, and diet and daily life during the administration period were maintained substantially the same as before the administration. After the administration is finished, through observation, inquiry and self-complaint combination and comprehensive evaluation, 5 people with unchanged qi deficiency performance and the disappearance of qi deficiency performance of other people (the significant improvement rate of qi deficiency reaches 97.3%), 13 people with unchanged blood deficiency performance and the disappearance of blood deficiency performance of other people (the significant improvement rate of blood deficiency reaches 94.5%), 14 people with unchanged aging performance and the significant reduction of aging performance of other people (the aging delay rate reaches 93.1%) are obtained. These results show that the composition of the present invention has excellent effects of improving qi and blood functions of human body and delaying aging of human body.

Test example 5: examination of Effect of composition on improving Immunity

Immunization is a biological response process by which the body "recognizes" and "eliminates" non-native antigens to maintain physiological homeostasis in the body. The immunity function is the basis of human health, and when the immunity function is disordered and low, the immunity function can reduce the infection resistance of the organism, reduce the capacity of identifying and eliminating self-aged histiocyte, and reduce the capacity of killing and eliminating abnormal mutant cells in the body, thereby reducing the disease resistance and self-healing capacity of the human body. In modern society, the pace of life is accelerated, and the competitive pressure is increased, so that many people are in a nervous working and learning state, and the organism can inhibit the immunologic function after being in the nervous state for a long time; meanwhile, more people have to eat convenient fast food due to intense work and study, unbalance of nutrients in the body is caused, and if the body is in the state for a long time, the immunity of the body is reduced, and finally the sub-health state of the body is caused. The immunity is a protective physiological response of the body, and the balance and stability of the internal environment are maintained through the immune function, while the immune diseases are caused by the abnormal immune function. According to the research of the American immune scientist, most of the diseases of human beings are attributed to the problems of the immune system. Long-term mental stress has an important influence on the immune function of a human body, and professor thomas of the Hopkins medical college of America observes 1337 volunteers for 18 years, and finds that if a person is in an isolated, contradictory, disappointing and depressed state for a long time, the balance of the internal environment is influenced, so that the resistance is weakened. In modern cities, the health of each person is easily threatened, including air pollution, water pollution, environmental pollution, working pressure, economic pressure, improper diet, bacteria and viruses, and all the factors which are unfavorable for health can cause low immunity of the organism, and are generally expressed as sub-health conditions of people such as incapability of concentrating, memory decline, frequent lassitude, susceptibility to diseases, early aging and the like. Particularly, some people who take mental labor as occupation have large relative mental stress, so that the mental stress is accumulated for a long time, and the brain is overloaded and operated, thereby causing the immunity to be reduced, the whole body to be weak, the head to be dizzy and the eyes to be astringent, the palpitation to be short of breath, the insomnia to be forgetful, and the like. People with low immunity are susceptible to cold and epidemic diseases, people with low immunity are easy to infect the people with low immunity for a long time than healthy people, and bacteria, viruses and the like can be gathered in the body to cause diseases of the human body due to the damage of the immune system caused by any reason. The immune system in the human body is the best defense weapon, which has the function of defending against the invasion of pathogenic microorganisms and the like.

The test examples examine the effect of the composition of the present invention on the immunoregulatory function of mice, and the specific tests are as follows. Reagent and grouping: the test animals were divided into 7 groups including: a blank control group (water was added), an acer palmatum crystal group (167mg/kg), a composition group of example 1, a composition group of example 6, a composition group of example 7, a composition group obtained in example 8 with reference to example 1, and a composition group obtained in example 9 with reference to example 1; the five compositions of the invention are respectively administered with the dosage of 100mg/kg body weight/day based on hemin; the test method comprises the following steps: a method of '4.1 load swimming test' according to Schweitianxin literature (Schweitianxin, et al, Tiepi Fengchi crystal anti-fatigue effect test, Zhejiang preventive medicine, 2002, 14 (11): 80); as a result: the mean values of the swimming time under load of the blank control group (water) were 268 ± 148 seconds, the mean values of the swimming time under load of the dendrobium candidum group (167mg/kg) were 862 ± 276 seconds (, respectively, the mean values of the swimming time under load of the composition group of example 1 were 1223 ± 293 seconds (, respectively), the mean values of the swimming time under load of the composition group of example 6 were 1441 ± 316 seconds (, respectively), the mean values of the swimming time under load of the composition group of example 7 were 1367 ± 252 seconds (, respectively), the mean values of the swimming time under load of the composition group of example 8 and example 1 were 515 ± 242 seconds (, respectively), and the mean values of the swimming time under load of the composition group of example 9 and example 1 were 469 ± 213 seconds (, respectively) compared with the blank control group, <0.1, <0.05, <0.01 ]. The result shows that the composition of the invention has excellent biological effect, has very obvious difference compared with a blank control group, has better effect than the control drug of the dendrobium candidum crystal, has excellent anti-fatigue effect, and the long-term effect of the anti-fatigue effect lies in the improvement of immunity and the elimination of sub-health problems.

Test example 6: examination of Effect of the composition on improving microcirculation

The effect of the inventive composition on improving microcirculation was observed using a MoorVMS-LDF2 laser doppler blood flow monitor. Animals and groups: 60 male mice with the weight of 18-20 g are randomly divided into 6 groups, and each group comprises 10 animals; each group was fed with standard meals and free drinking water; a, B, C, D, E groups were fed daily with the compositions of examples 1, 6 and 7 and the compositions of examples 8 and 9 obtained by the method of example 1, respectively (daily dose of each group was 5mg/kg body weight in terms of iron), and the animals in the S group of the control group were not fed with the composition as a control. The test was performed 30 days after the 6 groups of animals were dosed or fed. Animal preparation: injecting 40mg/kg pentobarbital sodium into the abdominal cavity of a mouse for anesthesia, cutting the skin in the middle of the head, removing surface tissues, grinding the skull at the top of the left temporal vertex to be thinner to a visible cerebral blood vessel under the skull by using a dental drill, fixing a laser probe of a laser Doppler blood flow monitor in the middle of the left temporal vertex bone, setting a time value for 0.3s, amplifying by 10 times, starting timing after stabilizing for 20min, observing for 0min, 30min and 60min, expressing microcirculation microcell blood flow by using a voltage value (mv), calculating three-point blood flow mean values of three observation time points of each animal, and calculating the three-point blood flow group mean value of 10 animals according to the mean value. As a result: the mean value of the blood flow group after feeding the S group for 30 days is 26.2 mv; A. the mean values of the blood flow group after the B, C groups of animals took the composition of the invention for 30 days were 39.8mv (increased by 51.9%, compared with the S group), 41.3mv (increased by 57.6%), and 38.3mv (increased by 46.2%); D. the mean values of the blood flow group after 30 days of taking the composition of the invention by the animals in the E group are 30.6mv (16.8 percent increase) and 29.7mv (13.4 percent increase) respectively. It can be seen that the composition of the present invention exhibits excellent microcirculation improving effect.

Test example 7: protective effect of composition on rat ovarian function

The ovary is a relatively radiation-sensitive area in the female reproductive system, and the damage of the ovary function is increased along with the increase of the irradiation dose. Ovarian dysfunction is a major long-term complication in patients receiving radiotherapy or chemotherapy, and large-dose and long-term chemotherapy can damage ovarian function of patients of all ages, resulting in amenorrhea, and reproductive capacity reduction or loss. Establishing an effective animal model for discussing and protecting the ovarian function has very important significance. People usually evaluate the ovarian function according to the regularity of the estrus cycle of rats, however, the methods are long in time, not beneficial to quickly evaluating the ovarian function and not beneficial to quickly evaluating the effect of the medicine on protecting the ovarian function. The ovarian function damage caused by exposure to radiation can cause endocrine dysfunction and reproductive function reduction, and symptoms such as menstrual disorder, amenorrhea and the like often appear after a large dose of radiation (such as radiotherapy) exposure of women. In the experiment, a medical linear accelerator is used for irradiating rats systemically to prepare a model of hypoovarial function of rats caused by radiotherapy, and the protective effect of the composition on ovarian function damage caused by radiotherapy is researched on the rat model. The experimental radiation has the characteristics of intuition and high efficiency in evaluating the effect of the medicine on the damage of the rat ovary function.

The test method comprises the following steps: clean SD female rats (weight 180-200 g), which are fed with granulated feed and freely fed, have room temperature of 20-25 ℃, relative humidity of 45-55 percent and are irradiated for 12h every day, after the rats are raised for 3d and are familiar with the environment, vaginal secretion smears are taken 8a day to observe a sexual cycle, and animals with a normal sexual cycle are selected for experiments. 35 qualified rats are selected and divided into five groups at random: (a) control group, (b) radiation group (i.e., RT group), (c) RT + composition group of example 1, (d) RT + composition group of example 6, and (e) RT + composition group of example 7. The animals were further fed under the above conditions, wherein the compositions were administered daily to the groups (c), (d) and (e) (daily dose of the composition in each group was 5mg/kg body weight in terms of iron), and after 45 days of feeding, four groups (b) to (e) were defined by reference to LiCaberus canescens et al [ LiCaberus canescens, et al. [ J ]. third Jun university medical science, 2008, 30(6): 506) 510] and each animal was irradiated with 200cGy rays at a speed of 50cGy/min, a field of irradiation of 30 cm. times.30 cm and a distance of 150 cm. After the rats in each group are irradiated by rays, vaginal secretion smear is taken every day, the estrus period is observed by a photoscope, the rats are killed in the estrus period 2 weeks after irradiation, and blood is taken from the aortic arch. Two ovaries, the right ovary fixed with 4% paraformaldehyde and the left ovary stored in a liquid nitrogen tank were taken. E2 and FSH were measured in rat serum by ELISA. Blood is collected from rat aortic arch, serum is separated, and the procedures are carried out according to ELISA kit operation instructions of AMEKO reagent company. Histomorphometry and follicle count: right-side ovary paraffin embedding, HE staining after slicing the largest cross section, counting the number of follicles with normal follicle structure under a light microscope, and counting primordial follicles, primary follicles, secondary follicles and mature follicles of each group of rats respectively. caspase3 assay: the activity of caspase3 was determined spectrophotometrically in the rat left ovarian tissue. Since caspase3 catalyzes the substrate Ac-DEVD-pNA to produce yellow substance pNA, caspase3 activity can be measured by measuring pNA absorbance at 405 nm. The kit was purchased from Biyuntian Biotech company according to the kit instructions. All indices were statistically analyzed using SPSS 18.0 software. The detection result of the measured data is expressed by mean +/-standard deviation (x +/-s); comparisons between sets of means were performed using One-Way analysis of variance (One-Way ANOVA); pairwise comparison between groups, and adopting an LSD method for inspection when the homogeneity of the variances is met; if the variances are not uniform, pairwise comparison is carried out by using a conservative Tambane's T2 test based on a t test, and the difference is statistically significant when P is less than or equal to 0.05.

And (3) test results: rat blood E2 level after irradiation (pmol/L): 6.93 plus or minus 0.58 for the control group, 2.71 plus or minus 0.44 for the RT group, 5.34 plus or minus 0.37 for the RT + example 1 group, 4.92 plus or minus 0.49 for the RT + example 6 group, and 5.56 plus or minus 0.68 for the RT + example 7 group; rat blood FSH levels after radiation exposure (ng/L): 0.323 plus or minus 0.021 in control group, 0.642 plus or minus 0.017 in RT group, 0.416 plus or minus 0.022 # in RT + example 1 group, 0.451 plus or minus 0.025 # in RT + example 6 group, and 0.427 plus or minus 0.013 # in RT + example 7 group; total number of follicles (number) in rats after irradiation with radiation: 22.43 ± 2.21 for control, 10.32 ± 2.18 for RT, 19.73 ± 1.93 # for RT + example 1, 20.12 ± 1.88 # for RT + example 6, and 18.47 ± 2.33 # for RT + example 7; change in caspase3 activity in rat ovarian tissue (characterized by pNA at 405nm A): 0.133 ± 0.042 for control, 0.576 ± 0.044 for RT, 0.303 ± 0.024 # for RT + example 1, 0.297 ± 0.046 # for RT + example 6, and 0.317 ± 0.051 # for RT + example 7; rat ovarian tissue change under light microscopy: the ovary structure of the control group is clear, primordial follicles, follicles in all levels of development and mature follicles can be seen in the ovary; the ovary of the RT group has thickened cortex, disordered structure and interstitial fibrosis, the number of original follicles in the cortex is sparse, the number of follicles growing at all levels and mature follicles is reduced sharply, and a large number of atretic follicles and a plurality of large old corpus luteum tissues are found; the ovaries of three animals given the composition were clear, primordial follicles were visible in the ovaries, developing follicles and mature follicles at all levels, and a small number of atretic follicles and luteinizing substances were visible; of the above results, P <0.05 compared to control group and # P <0.05 compared to RT group.

The above results indicate that the composition of the present invention can prevent the damaging effects of radiation on ovarian function, and is useful for enhancing female ovarian function, and in view of the fact that enhancing female ovarian function as described above can be reflected in the improvement of female skin, the composition of the present invention can also improve female skin, for example, prevent facial yellowing, dry skin, loose and rough skin, and the like.

Test example 8: observation of the Effect of the composition on iron intake and supplementation by pregnant women, lying-in women and lactating mothers

In the test, 38 pregnant women voluntarily took the composition of the invention in the first 30-60 days before pregnancy and took 200mg of hemin per day until the end of lactation, monitored hemoglobin (Hb) and/or Red Blood Cells (RBC) before pregnancy, 2 weeks after pregnancy, 4 weeks after pregnancy, 8 weeks after pregnancy, 4 months after pregnancy, 7 months after pregnancy, 2 months before birth, 6 months after birth, 2 months after baby and 6 months after baby, and the results showed that Hb was 117-142 g/L and RBC was (442-487) × 10¹⁰In the/L range, Hb is 176-191 g/Hb in all newborns during the whole monitoring processL range and no anemia appearance was observed throughout the observation/monitoring of all mothers and newborns. These results indicate that the composition of the present invention exhibits excellent iron-supplementing effects to mothers and newborns, and thus the product is expected to effectively improve the physiological effects of body functions of pregnant women, lying-in women, lactating mothers, fetuses and newborns.

Test example 9: examination of Effect of the composition on inhibiting arteriosclerosis

Cardiovascular and cerebrovascular diseases are frequently encountered diseases and seriously harm human health, Arteriosclerosis (AS) is the main pathological basis of ischemic cardiovascular and cerebrovascular events, and atherosclerosis can be gradually developed into coronary artery and cerebrovascular diseases if effective intervention is not clinically performed. To examine the effect of the composition of the present invention on inhibiting arteriosclerosis, the test example observed the effect of the composition of the present invention on rat AS formation, particularly its inhibitory effect, by replicating the rat model of AS. Reagents and reagents: the compositions of examples 1, 6 and 7 of the present invention (daily dose of each group was 5mg/kg body weight in terms of iron), atorvastatin calcium (daily dose was 2mg/kg body weight); vitamin D3 injection, Freund's complete adjuvant, ovalbumin, commercially available. Total Cholesterol (TC), Triglyceride (TG), high density lipoprotein cholesterol (HDL-c), low density lipoprotein cholesterol (LDL-c) kits, commercially available. Superoxide dismutase (SOD), Malondialdehyde (MDA), Nitric Oxide (NO), Nitric Oxide Synthase (NOS) kit, commercially available. Interleukin-18 (IL-18), soluble CD40L (sCD40L), Adiponectin (APN) Elisa enzyme kit, commercially available. Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), Endothelin (ET) radioimmunoassay kit, commercially available.

The experimental method comprises the following steps: taking 60 SPF SD rats, male SD rats and 180-200 g of body mass, wherein the rats are randomly divided into six groups: (a) blank control group, (b) model control group, (c) composition of example 1, (d) composition of example 6, (e) composition of example 7, and (f) atorvastatin calcium group. The reference document performs atherosclerosis model replication on the other five groups except the blank control group [ Wangwei, etc.. the influence of the salvia miltiorrhiza and hawthorn drug on the atherosclerosis of rats [ J ]. Chinese traditional medicine J2011, 36(6): 784-789; peri-red, et al, comparison of three doses of vitamin D3 in combination with high fat diet to establish a model of atherosclerosis in rats [ J ]. journal of chinese arteriosclerosis, 2012, 20 (11): 995-998]. The animals in each group were fed normal pellet diet from day 0, and the rest five groups of rats were fed high fat diet (formula: 2% cholesterol, 10% lard, 5% white sugar, 0.3% sodium cholate, 5% egg yolk powder, 0.2% propylthiouracil, 77.5% basal diet). Experimental 15D, 45D and 75D high-fat feed animals respectively showed 360 ten thousand U/kg, 10 ten thousand U/kg and 10 ten thousand U/kg of ip vitamin D. And the first day of ip vitamin D3 was used for the immunization damage of rats in the high-fat diet group. During the experiment, the rats were observed daily for general signs of drinking, appearance, activity, etc. The body mass of the rat is weighed every week, and the gavage amount is adjusted. Each group of rats was administered the drug starting on day 0 and gavage continued for 90 d. After 1 hour of the last administration, rats are respectively anesthetized with 0.3mL/100g of 10% chloral hydrate, abdominal aorta is subjected to blood sampling, serum is separated, TC, TG, LDL-C, HDL-C and Ca are detected by a full-automatic biochemical analyzer, the arteriosclerosis index is calculated, SOD and NOS are detected by a colorimetric method, MDA is detected by a TBA method, NO is detected by a nitrate reductase method, ET, IL-6 and TNF-alpha are detected by an radioimmunoassay, and IL-18, sCD40L and APN are detected by an Elisa method. Weighing the weight of the heart and the liver, calculating the index of the viscera, taking the thoracic aorta, carrying out conventional fixed dehydration, HE staining and carrying out pathological histological observation. All experimental data were statistically analyzed using SPSS 16.0 software. The measured data are tested by a one-factor analysis of variance F, the test level alpha is 0.05, and the difference is statistically significant when P is less than 0.05. The results of the experiments (both in average) are summarized below. (1) Effect of composition on AS model rat visceral index, arteriosclerosis index: the organ index and arteriosclerosis index of each group of rats [ xushuyun, etc., pharmacological experimental methodology [ M ], third edition, Beijing: national health publishing agency, 2005: 1205; yangqiyu, et al, Jianpi Huoxue san Chong san Zhu Tang for hyperlipemia clinical observation [ J ], Shanghai J.J. Med.2015, 49 (3): 46-48]. The results show that: the heart indexes among all groups have no difference among the groups, and the average value is in the range of 0.28-0.30 g/100 g; (a) the mean values of the liver indexes of the group (c) to the group (f) are respectively 2.36g/100g and 4.94g/100g and are obviously different from the mean values of the liver indexes of the group (b), and the mean values of the liver indexes of the four groups (c) to (f) are respectively in the range of 3.78-4.02 g/100g and are respectively obviously different from the mean values of the liver indexes of the group (b); (a) the mean values of Arteriosclerosis Indexes (AI) of the groups (b) are 0.81% and 7.11% respectively, and the two are significantly different, and the mean values of arteriosclerosis indexes of the four groups (c) to (f) are all in the range of 4.87-5.11%, and the four are significantly different from the group (b). (2) Effect of the composition on blood lipid levels in AS model rats: no difference in TG levels between groups; blank control TC of 1.35mmol/l, LDL-C of 0.52mmol/l, HDL-C of 0.79mmol/l, model control TC of 18.52mmol/l, LDL-C of 15.74mmol/l, HDL-C of 2.88mmol/l, significant differences between the two groups, consistent with literature reports [ Zhouyang, et al, J. arterosclerosis, China, 2012, 20 (11): 995 ]; (c) four groups of TC (9.47 to 11.21 mmol/l) and LDL-c (8.33 to 10.05 mmol/l) are respectively obviously different from the group (b). (3) Effect of the composition on serum MDA content in AS model rats: the blank control group MDA is 5.02nmol/l, the model control group MDA is 6.84nmol/l, and the two groups have significant difference; (c) the MDA in the four groups from (a) to (f) is in the range of 3.87-4.13 nmol/l, and the four groups are respectively obviously different from the group (b). (4) Effect of the composition on vasoactive substances in rats AS model: the result shows that compared with the blank control group, the serum NOS content of the rats of the model control group is reduced, the ET content is increased and has obvious difference (P <0.05), and the serum NO content is also lower than that of the blank control group but has NO statistical significance; compared with a model control group, the composition group can obviously improve the serum NO level and the NOS level of a model rat and can obviously reduce the ET content (P <0.05) of the serum of the model rat. (5) Effect of the composition on serum cytokines in rat model AS: the result shows that the detection values of TNF-alpha, CPR, IL-18 and sCD40L of the serum of the rat in the model control group are all higher than those of the rat in the blank control group, the APN content is reduced and has significant significance, and the mean value of IL-6 of the serum also has an increasing trend; compared with a model control group, each composition and the atorvastatin calcium group can obviously reduce the levels of serum TNF-a, IL-6 and IL-18 of AS rats and the level of sCD40L, and improve the APN content of the serum of the rats with obvious difference. These results indicate that long-term administration of the composition of the present invention will help to intervene or slow down the progression of arteriosclerosis by lipid lowering, anti-inflammatory, reducing oxygen radical damage, etc.

It will be evident to those skilled in the art that the invention is not limited to the details of the foregoing illustrative embodiments, and that the present invention may be embodied in other specific forms without departing from the spirit or essential attributes thereof. The present embodiments are therefore to be considered in all respects as illustrative and not restrictive, the scope of the invention being indicated by the appended claims rather than by the foregoing description, and all changes which come within the meaning and range of equivalency of the claims are therefore intended to be embraced therein.

Claims (8)

1. The application of the pharmaceutical composition in preparing the medicine for improving the body functions of pregnant women, lying-in women, nannies and fetuses, wherein the pharmaceutical composition comprises 100 parts by weight of hemin, 100-1200 parts by weight of diluent and 2-20 parts by weight of phospholipid; the diluent is selected from: starch, sucrose, lactose, microcrystalline cellulose, calcium hydrogen phosphate; the phospholipid is selected from: egg yolk lecithin, soybean lecithin; the pharmaceutical composition is prepared by the following steps:

pre-pulverizing hemin into fine powder capable of passing through 100 mesh sieve; dissolving phospholipid in ethanol to prepare a solution with the concentration of 20-25%; spraying a phospholipid solution into the fine hemin powder in a fluidized state in a fluidized bed granulator at the temperature of 30-35 ℃, and continuously fluidizing to remove ethanol; adding 20-30 parts by weight of diluent, uniformly mixing, and pressing the materials into a sheet-shaped object by using an extruder; the sheet-shaped object is put at-20 to-15 ℃ and frozen for 24 to 30 hours; crushing the sheet, adding the rest of the diluent, uniformly mixing, and continuously crushing into fine powder which can pass through a 60-mesh sieve to obtain the composition.

2. The use according to claim 1, wherein the pharmaceutical composition comprises 100 parts by weight of hemin, 100 to 750 parts by weight of diluent, and 5 to 15 parts by weight of phospholipid.

3. The use according to claim 1, wherein the pharmaceutical composition comprises 100 parts by weight of hemin, 100-500 parts by weight of diluent, and 5-10 parts by weight of phospholipid.

4. The use according to claim 1, wherein the pharmaceutical composition comprises 100 parts by weight of hemin, 300 parts by weight of diluent and 7.5 parts by weight of phospholipid.

5. Use according to claim 1, wherein the composition obtained when preparing the pharmaceutical composition is further prepared in the form of a formulation selected from the group consisting of: tablet, hard capsule, soft capsule, pill, powder, granule, oral suspension, dry suspension, unguent, and jelly.

6. The application of a pharmaceutical composition in preparing a medicament for improving the body functions of a pregnant woman, a lying-in woman, a lactating mother and a fetus, wherein the pharmaceutical composition comprises 100 parts by weight of hemin, 1200 parts by weight of lactose serving as a diluent and 1 part by weight of soybean phospholipid; the pharmaceutical composition is prepared by the following steps:

pre-pulverizing hemin into fine powder capable of passing through 100 mesh sieve; dissolving phospholipid in ethanol to obtain 25% solution; spraying phospholipid solution into fluidized hemin fine powder in fluidized bed granulator at 30 deg.C, and further fluidizing to remove ethanol; adding 20 parts by weight of diluent, uniformly mixing, and pressing the materials into a sheet-shaped object by using an extruder; freezing the pellet at-15 deg.C for 30 hr; crushing the sheet, adding the rest of the diluent, uniformly mixing, and continuously crushing into fine powder which can pass through a 60-mesh sieve to obtain the composition.

7. A method for preparing a pharmaceutical composition, which comprises 100 parts by weight of hemin, 1200 parts by weight of lactose serving as a diluent and 1 part by weight of soybean lecithin; the method comprises the following steps: pre-pulverizing hemin into fine powder capable of passing through 100 mesh sieve; dissolving phospholipid in ethanol to obtain 25% solution; spraying phospholipid solution into fluidized hemin fine powder in fluidized bed granulator at 30 deg.C, and further fluidizing to remove ethanol; adding 20 parts by weight of diluent, uniformly mixing, and pressing the materials into a sheet-shaped object by using an extruder; freezing the pellet at-15 deg.C for 30 hr; crushing the sheet, adding the rest of the diluent, uniformly mixing, and continuously crushing into fine powder which can pass through a 60-mesh sieve to obtain the composition.

8. The method according to claim 7, wherein the resulting composition is further formulated as a soft capsule.